The burden of neoplastic diseases is a significant global health claiming accounting for thousands of deaths. In Republic of uganda, about 32,617 cancer cases were reported in 2018, accompanied past 21,829 deaths. In a view to identify some potential anticancer plant candidates for possible drug development, the current written report was designed to compile the inventory of plants with reported anticancer activity used in rural Republic of uganda and the evidences supporting their utilise in cancer therapy. An electronic survey in multidisciplinary databases revealed that 29 plant species belonging to 28 genera distributed amongst 24 families take been reported to be used in the management of cancer in Uganda. Anticancer plants were majorly from the families Bignoniaceae (7%), Caricaceae (7%), Fabaceae (seven%), Moraceae (7%), and Rutaceae (seven%). Well-nigh species occur in the wild (52%), though some are cultivated (48%). The growth habit of the plants is every bit copse (55%) or herbs (45%). Anticancer extracts are normally prepared from leaves (29%), bawl (24%), roots (21%), and fruits (xiii%) through decoctions (53%), as food spices (23%) or pounded to produce ointments that are applied topically (x%). Prunus africana (Hook.f.) Kalkman, Opuntia species, Albizia coriaria (Welw. ex Oliver), Daucus carota L., Cyperus alatus (Nees) F. Muell., Markhamia lutea (Benth.) M. Schum., and Oxalis corniculata L. were the most frequently encountered species. As per global reports, Allium sativum 50., Annona muricata L., Carica papaya 50., Moringa oleifera Lam., Opuntia species, Prunus africana (Hook.f.) Kalkman, and Catharanthus roseus (L.) G. Don. are the most studied species, with the latter having vincristine and vinblastine anticancer drugs developed from it. Prostate, cervical, breast, and skin cancers are the acme traditionally treated malignancies. There is a need to isolate and evaluate the anticancer potential of the bioactive compounds in the unstudied claimed plants, such as Cyperus alatus (Nees) F. Muell., Ficus dawei Hutch., Ficus natalensis Hochst., and Lovoa trichilioides Harms, and elucidate their mechanism of anticancer activity.
1. Introduction
Cancer ascribes a collection of diseases triggered by the uncontrolled proliferation of cancerous cells. It is a global health brunt that has left anintolerable death cost worldwide. Conservative estimates indicate that cancer (of the liver, breasts, lungs, cervix uteri, breadbasket, and colorectal) causes about thirteen% of annual deaths globally [one]. In Uganda, in that location have been reports on cancer cases, though collected data are not normally coherent [two]. The commonest types of cancer encountered in Uganda include cervical, prostate, breast, lung, and skin cancers, Kaposi sarcoma, Burkitt'south lymphoma, and cancer of the bone, eye, colon, and blood (leukemia) [iii]. Betwixt 1952 and 1953, 796 cases of cancer were reported in Uganda, 15 of which were stage IV cases of cancer of the cervix uteri [four]. The 1990s recorded Kaposi sarcoma, prostate, and oesophageal cancers among men and Kaposi sarcoma, cervical, and breast cancers among women equally the most prevalent cancers in Republic of uganda [5].
The eruption of the ill-fated virus (HIV) and the AIDS epidemic led to an unprecedented increase in the incidences of Kaposi sarcoma, squamous jail cell carcinoma of the conjunctiva, and not-Hodgkin's lymphoma in the penultimate year [6]. Cervical cancer, the quaternary well-nigh prevalent cancer globally, later registered an alarming relative frequency in Uganda, with 3, 915 new cases and 2, 275 annual deaths reported [7, 8]. The state of affairs is complicated by the fact that very few (averagely less than 10% of the 10.22 million susceptible Ugandan females) accept been screened for cervical cancer [7, 9]. Reluctancy to screen, stigma, lack of awareness, chronic poverty, and inadequate medical services are largely responsible for the magnitude of the cancer epidemic in Republic of uganda [9–xi]. Thus, most cancer cases registered in hospitals are usually in their advanced stages that cannot be treated optimistically [12, 13].
Cancer trends for two decades (1991–2010) in the Kampala cancer registry have indicated that there has been an increment in cancer cases, peculiarly for chest cancer and prostate cancer in women and men, respectively [14]. On the other paw, the incidence of the oesophagus, liver, and big bowel (colon, rectum, and anus) cancers has remained relatively constant [fourteen]. According to a recent report based on Gulu and Kampala cancer registries [15], 32,617 cancer cases were registered in the state in 2018 and nigh 21,829 of these victims succumbed to death. In Uganda, the survival of cancer patients is alarmingly deplorable in comparison to other non-African third earth nations [2, 16]. The risk factors cited for the loftier cancer incidences in Uganda include acquisition from family lines, hormonal imbalances, consumption of mycotoxin (aflatoxin) contaminated foods, exposure to chemicals, irradiation, viruses, and bacteria [3, 17–19].
Conventional therapies for the direction of cancer have several side effects due to their lack of specificity and are limited in rural settings [20]. Further, the sturdy resistance of cancerous cells to cytotoxic and antineoplastic drugs has presented a fresh challenge, giving unsatisfactory ministration outcomes and capricious resistance to antineoplastic agents [21, 22]. Coupled with the prohibitive costs, unavailability of allopathic drugs, and chronic poverty in Uganda, in that location is a demand to fold back on habitation grown solutions, exploring flora and fauna [23]. Uganda, the pearl of Africa, is role of the East African botanical block and is blessed with over 6,000 plant species [24, 25]. Plants are regaining shape and emerging as an integral function of the ethnomedical approach for the management of diseases in Uganda [26]. The near cathartically notable anticancer botanical species in Republic of uganda are Prunus africana (Hook.f.) Kalkman and the periwinkle plant (Catharanthus roseus (L.) G. Don) from which antitumor drugs vinblastine and vincristine take been adult [23, 27]. Over 5,000 phytochemicals such as phenolics, carotenoids, glucosinolates, terpenoids, and alkaloids from over 3,000 institute species have been reported to be primal actors in cancer therapy [28–30]. In Uganda, anecdotal reports reveal that there exists a puddle of plants utilized locally for the management of cancer [23]. Indeed, information on indigenous medicinal plants used for various maladies has been reported by preceding authors, but none of them scrutinized anticancer plants. This review seeks to obtain a list of medicinal plants reported by ethnobotanical surveys in Republic of uganda equally anticancer plants and identify the agile phytochemicals in the claimed plants and the anticancer studies done on them as per global studies. Potential candidates from this review which are scantily studied will be investigated in penultimate studies.
two. Methodology
A comprehensive literature search was performed in Scopus, Web of Science Cadre Collection, PubMed, Science Direct, Google Scholar, and Scientific Electronic Library Online (SciELO) from Baronial 2019 to November 2019 following procedures previously employed elsewhere [26]. The search was performed independently in all databases. The report databases included original articles published in peer-reviewed journals, books, thesis, dissertations, patents, and other reports covering anticancer plants, dated until Nov 2019. All publishing years were considered, and articles with data on cancer or medicinal plants in Republic of uganda were given utmost priority. Thus, references independent within the returned results were assessed concerning their inclusion in this study, and farther searches were carried out at the Google search engine using more than full general search terms, to augment the search, as follows: words cancer, plants, establish extract, vegetal, vegetal species, vegetal extract, traditional medicine, alternative medicine, complementary therapy, natural medicine, ethnopharmacology, ethnobotany, herbal medicine, herb, herbs, decoction, infusion, macerate, malignant, hepatocellular carcinoma, carcinoma, prostate cancer, breast cancer, Kaposi sarcoma, Burkitt'south lymphoma, cancer of the bone, cancer of the heart, cancer of the colon, cancer of the blood, leukemia, anticancer, cancer of the cervix uteri, lung cancer, liver cancer, skin cancer, and Uganda were used. The terminal search was done on 25thursday November 2019. The search outputs were saved where possible on databases and the authors received notification of any new searches meeting the search criteria from Science Directly, Scopus, and Google scholar.
3. Results and Discussion
Only articles in English and local languages were considered. After the multidisciplinary database and Google search engine result assessments, 16 reports of interest specifically on the discipline of anticancer plants in Republic of uganda were retrieved (Table 1). The botanical names of the plants listed were vetted in botanical databases: The Institute List [47], International Plant Names Index (IPNI) [48], NCBI taxonomy browser [49], and Tropicos [50]. Where a given species was considered as distinct species in dissimilar reports, the nomenclature as per the botanical databases above took precedence in the review. The botanical families used, the establish local names (Lango, Ateso, Luganda, Rukiga, Rutoro, Lusoga, Lugisu, Ngakarimojong, and Lugbara), the life forms, office(s) used, conservation status, preparation and assistants fashion, and the districts where the plants were reported are captured (Table ane). On anticancer potential, species studied as per global reports, the active phytochemicals reported and tested with positive results in the plant species identified by this review are reported (Table two; Figure 1). A brief review of other ethnomedical uses of the reported species equally per Ugandan and global studies is also presented (Table 3).
Cytotoxicity of extracts reported against chest cancer (MCF-vii), hepatocellular carcinoma (HepG2), and cervical carcinoma (HeLa) prison cell lines [51]. Isoquercitrin inhibited urinary bladder, pancreatic, and colon cancer progress [52–54]
Extracts induced pregnant cell growth inhibition (63%) in man chest cancer (MCF-7) and skin fibroblast (CCD-1059 sk) cells. The expression of proapoptotic caspase-3, caspase-9, and p21 genes was increased in MCF-7 cells [55]
Albizia coriaria (Welw. ex Oliver)
Oleanane-type saponins (coriarioside A and coriarioside B), gummiferaoside C, acacic acid glycosides, lupeol (3), lupenone, betulinic acid, acacic acrid lactone, (+) – catechin, and benzyl alcohol [56–58]
Cytotoxicity (IC50 > 500μone thousand/ml) confronting human embryonic lung fibroblast (HELF) cells [59]. Coriarioside A and gummiferaoside C from root bark showed cytotoxicity against two colorectal man cancer cells: HCT116 (with IC50 of iv.2μM for coriarioside A and 2.viiμM for gummiferaoside C) and HT-29 (with IC50 6.sevenμThousand for coriarioside A and 7.9μGrand for gummiferaoside C) cell lines [56]
Extracts exhibited an antiproliferative consequence on human cancer cell lines, including liver (HepG2), colon (Caco2), prostate (PC-3), and breast (MCF-seven) cancer cells [61]. Extracts induced G2/M-stage cell wheel arrest in EJ bladder cancer cells [62]. DATS suppressed the proliferation of SGC-7901 gastric cancer cells [63]
SAC induced cell cycle arrest in A2780 human epithelial ovarian cancer cells [64]. S-propargyl-l-cysteine (SPRC), an analogue of SAC, reduced the proliferation of homo pancreatic ductal adenocarcinoma cells and induced prison cell bike arrest [65]. Garlic derived S-allylmercaptocysteine (SAMC) suppressed the proliferation of hepatocellular carcinoma cells [66]. SAMC inhibited the proliferation of man colorectal carcinoma SW620 cells [67]
Allicin inhibited the proliferation of gastric adenocarcinoma cells past inducing prison cell cycle abort [68]. Ajoene was shown to restrain the growth of glioblastoma multiforme cancer stem cells and human breast cancer cells [69]
Annonaceous acetogenins exhibited antiproliferative activity against human prostate cancer PC-3 cells [70]. Fruit extracts are cytotoxic against U937 histiocytic lymphoma prison cell lines with IC50 of 10.5, 18.two, and 60.9μg/ml for ethyl acetate, hexane, and methanol extracts respectively [74]
Annonacin caused complete suppression of seven,12-dimethylbenz[a]anthracene (DMBA) induced and 12-0- tetradecaboylphorbol-13-acetate (TPA) promoted skin tumorigenesis in mice [75]
At 0.1μK, annonacin induced growth arrest and apoptosis in breast cancer (MCF-7) cells [76]
Annomuricin E was cytotoxic to HT-29 colon carcinoma and CCD841 normal colon jail cell lines with ICfifty values of 5.72, 3.49, and 1.62μm/mL for HT-29 cells at fourth dimension intervals of 12, 24, and 48 hours of assistants, respectively [77]
Stem extracts suppressed the expression of molecules associated with hypoxia and glycolysis in CD18/HPAF (pancreatic) cancer cells (IC50 of 73.0μg/mL) [78]
Aqueous leaf extracts exhibited anticancer action with ICfifty values of 220, 350, and 250μg/mL for breast cancer cell lines: MCF7, MDA-MB231, and 4T1, respectively [79]. Foliage extracts recorded cytotoxicity against human being bladder cancer (K562) and leukemia cancer (ECV304) prison cell lines [80]
Cytotoxicity recorded confronting Raji cells with ICfifty values of ninety.6, 407.2, and 260.twoμgrand/mL. Cytotoxic consequence of chloroform and due north-hexane extracts on HeLa cell lines gave IC50 values of 127.3 and 169.2μk/mL, respectively [81]
Leaf extracts inhibited cell proliferation in pancreatic cancer cells (capan-1) [82]
Ethanol excerpt of seeds showed a cytotoxic issue on MDBK and HEp-2 cells (ICfifty values:34.five and 55 mg/mL, respectively) at 24 h, and an ICl value of 49.vi × x−3 mg/mL toward HEp-two cells at 72 h [83]
Cytotoxic against kidney epithelial (VERO), stomach cancer (C-678), and homo large lung cell carcinoma (H-460) jail cell lines with IC50 values lower than 0.00022 mg/mL for all the cell lines [84]. Cytotoxicity was reported against histiocytic lymphoma cell lines (U937), pancreatic cancer cells (FG/COLO357), chest cancer cells (MDA-MB-435S), immortalized human keratinocytes (HaCat), normal human liver cells (WRL-68), and human being skin cancerous melanoma (A375) [73, 78, 85–87]. In histiocytic lymphoma jail cell lines, the extract had an IC50 value of 7.8μ1000/mL. Toxicity toward FG/COLO357 with an IC50 value of 200μm/mL [78]. Cytotoxic effect of due north-butanolic extract of leaves against MDA-MB-435S (homo breast carcinoma), HaCaT (man immortalized keratinocyte), and WRL-68 (normal human hepatic) jail cell lines with IC50 values of 29.2, 30.1, and 52.4μone thousand/mL, respectively [73]
Ethanol extracts of leaves cytotoxic to Ehrlich Ascites carcinoma (EACC) and breast cancer (MDA and SKBR3) prison cell lines with IC50 values of 335.85, 248.77, and 202.33μone thousand/mL [88]. Fruit extracts had substantial repression of breast cancer cells (MDA-MB-468) growth likewise every bit selective suppression of epidermal growth gene receptor (EGFR) with IC50 of four.8μg/mL [89]
Acetonitrile extract inhibited the viability of breast (MDA-MB-231 and MCF-7), pancreas (MIA PaCa-2), prostate (PC-three), and non-small-cell lung cancer (A459) cells. The extracts inhibited cancer cell proliferation, decreased tumor growth, and induced apoptosis in vivo in triple negative breast cancer (MDA-MB-231) xenografts grown on the chick chorioallantoic membrane (CAM) assay also every bit in nude mice [91]. Hydroalcoholic extract had a cytotoxic consequence in a dose-dependent manner against D-17 canine osteosarcoma cell lines better than pure artemisinin, indicating a possible synergistic effect of the phytocomplex and a machinery of action involving atomic number 26 and possibly ferroptosis [92]
The ethanolic extract exhibited pregnant anticancer activeness against lung cancer (A549) prison cell line just but a slight effect against colorectal adenocarcinoma (Caco-two) cell line at 800μg/mL [94]. Cytotoxicity against PC-3 cells led to a decrease in the growth rate of the cells (three.vii% in 3 days) at 29μone thousand/mL. Comparative cytotoxicity tests in normal homo peel (FC) and liver (HC) prison cell lines showed that the extracts were cytotoxic on the cells, though the action was lower than that of doxorubicin (8.six% compared to 100%, respectively, at 29μg/mL concentration in a 3-day test period) [95]
Leaves and stem bark extracts had LC50 of 539.half-dozen and 389.8μg/mL in brine shrimp toxicity [97]
Cannabis sativa L.
Δ9-tetrahydrocannabinol, THC (eighteen) [98]
THC and other cannabinoids exhibited antitumor effects in fauna models of cancer [99]. The acetone extract exhibited more than anticancer activity confronting chest adenocarcinoma (MCF-7), the glioblastoma (SF-268), and the colon adenocarcinoma (HT-29) cells [100]
Cytotoxicity test on leukemia (CCRF-CEM) cells at twoscoreμthou/mL showed that leaves and bawl extracts induced more 50% growth of this prison cell line. Fruit mesocarp oil excerpt and seed kernel oil extracts are expected to exist vital for chemoprevention of cancers and other oxidative damage-induced diseases [104]
Capsicum frutescens L.
Capsaicin (xx) and quercetin [105]
Aqueous fruit extracts exhibited anticancer activity (though lower than capsaicin standard) when tested against prostate (PC-3) and breast (MCF-7) cancer cell lines in vitro [105]
Pure lycopene and papaya juice inhibited the viability of liver cancer (HepG2) cell line with ICl of 22.8μone thousand/mL and xx mg/mL [108]. due north-hexane seed extract dose-dependently inhibited superoxide generation (IC50 = 10μg/mL) and the viability of acute promyelocytic leukemia (HL-60) cells (ICl = 20μg/mL), comparable to that of pure benzyl isothiocyanate [109]
Aqueous excerpt of mankind (0.01–4% five/v) inhibited the proliferation of chest cancer cell line (MCF-7) [110]. Ethanolic excerpt of the pericarp (50–640μchiliad/mL) inhibited the growth of breast cancer cell line (MCF-7) treated with sodium nitroprusside, a nitric oxide donor [111]. Chest cancer prison cell line (T47D) was inhibited past leaf poly peptide fraction with ICl = 2.8 mg/mL) and induced apoptosis by regulation of protein expression [112]
Aqueous extracts of leaves (1.25–27 mg/mL) exhibited a concentration-dependent anticancer effect on tummy cancer cell line (AGS), pancreatic cancer prison cell line (Capan-ane), colon cancer cell line (DLD-ane), ovarian cancer cell line (Dov-13), lymphoma cell line (Karpas), breast cancer prison cell line (MCF-vii), Neuroblastoma jail cell line (T98G), uterine cancer cell line (HeLa), and T-cell leukemia cell line (CD26 negative or negative Jurkat) jail cell lines and suppressed DNA synthesis by suppressing the incorporation of 3H-thymidine [113]
Aqueous extract of leaves (0.625–20 mg/mL) inhibited the proliferative responses of both haematopoietic and solid tumor cell lines (T-cell lines, H9, Jurkat, Molt-4, CCRF-CEM, and HPB-ALL), Burkitt's lymphoma jail cell lines (Ramos and Raji), chronic myelogenous leukemia cell line (K562), cervical carcinoma jail cell line (HeLa), hepatocellular carcinoma cell lines (HepG2 and Huh-7), lung adenocarcinoma jail cell line (PC-14), pancreatic epithelioid carcinoma jail cell line (Panc-i), mesothelioma cell lines (H2452, H226, and MESO-4), plasma cell leukemia jail cell line (ARH77), anaplastic big prison cell lymphoma cell line (Karpas-299), breast adenocarcinoma cell line (MCF-7), mesothelioma cell line (JMN), and pancreatic adenocarcinoma cell line (Capan-1). In peripheral blood mononuclear cells, the extract reduced the production of IL-2 and IL-4 whereas information technology increased the product of Th1 types cytokines such as IL-12p40, IL-12p70, INF- , and TNF- . The expression of 23 immunomodulatory genes was enhanced by the addition of papaya extract [114]
Leaf juice not simply exhibited a stronger cytotoxic effect on human squamous prison cell carcinoma (SCC25 cancer) cells but also produced a significant cancer-selective effect as shown by tests on noncancerous human keratinocyte HaCaT cells [115]
Cytotoxicity with LCfifty of 6.7μg/ml in brine shrimp assay [97, 118, 119]
Vindoline from foliage extracts was cytotoxic to HCT-116 colorectal carcinoma cell line at 200μg/mL [120]
Citrus reticulata Blanco, 1837
Limonin, isolimonexic acrid methyl ether, ichangin, deacetylnomilin, and obacunone [121]
In vitro tumor cytotoxicity of different varieties confronting gastric cancer jail cell lines (SGC-7901, BGC-823, and AGS) recorded IC50 ranging from 20.49 to 368.fortyμg/mL [122]. Antiangiogenic effect was reported [123]
Cymbopogon citratus (DC) Stapf
Citral (neral and geranial), geraniol and β-myrcene, 6-methyl-five-hepten-2-ane, and undeca-2-1 [124]. Oils contain geranial, neral, myrcene, and beta-pinene [125]
Essential oil exhibited protective action against N-butyl-N-(iv-hydroxibuthyl)nitrosamine-induced Deoxyribonucleic acid damage and a potential anticarcinogenic activity against mammary carcinogenesis in seven,12-dimethylbenz(a) anthracene, 1,2-dimethylhydrazine initiated female Balb/C mice [124]. In synergy with Taraxacum officinale root extract induced apoptosis in prostate cancer cells (DU-145 and PC-three). The everyman combination dosage of taxol treatment (0.01 μM with 0.01 mg/mL excerpt) showed comparable induction of apoptosis to the highest private treatment dosage of taxol (0.5μK) [20]
Chemopreventive against vii,12-dimethyl Benz(a)anthracene-induced squamous prison cell carcinoma in mice [126]. The aqueous extract has anticancer activity against human promyelocytic leukemia HL-threescore cells. Oil extract is chemopreventive against induced pare cancer [128]. Apoptosis was recorded with colon and breast human cancer cell lines; pentane oil fraction showed a cytotoxic result on human breast adenocarcinoma prison cell lines MDA-MB-231 and MCF-seven, causing cell cycle arrest and increased apoptosis mediated through the Erk pathway [129]
Elaeodendron buchananii (Loes.)
Steroidal glycosides, eudesmane-type sesquiterpenoid, and dammarane triterpenoids: elabunin (21) [130–132]
Elabunin exhibited moderate cytotoxic activity with a median effective dose (EDl) of 100μg/mL against L- 1210 leukemic cells [132]
Erythrina abyssinica Lam. ex DC.
Erythrina alkaloids: erythraline, erysodine, erysotrine, 8-oxoerythraline, and 11-methoxyerysodine [133]
Cytotoxicity with LCfifty value > 240 μg/ml [134]. In vitro cytotoxicity of the rough alkaloidal fraction reported against HeLa, Hep-G2, HEP-2, HCT-116, MCF-vii, and HFB4 cell lines with ICl values of 13.8, ten.one, 8.sixteen, 13.9, 11.4, and 12.iiμg/mL [133]
Euclea natalensis A.DC.
Mamegakinone, diospyrin (22) and 7-methyljuglone from root bawl, lupeol,-sitosterol, 20(29)-lupene-3-isoferulate, Isodiospyrin, 5-hydroxy-four-methoxy-2-nathaldehyde, fourscore-hydroxydiospyrin, neodiospyrin, methylnaphthazarin, euclanone, octahydroeuclein, shinanolone, diospyrin, and natalenone [135–137]
Cytotoxicity of ethanolic roots and stem extracts reported in brine shrimp lethality test [138]
Cytotoxicity of crude chloroform extract of the roots, diospyrin, and 7-methyljuglone reported against green monkey kidney cells (VERO) and a mouse macrophage cell line, J774A.ane. Crude extract and diospyrin had IC50 values of 64.87 and 17.78μthou/mL while 7-methyljuglone effected a 90% reduction of growth of Mycobacterium tuberculosis Erdman within J774.1 macrophage at 0.57μm/mL [139]
Cytotoxicity of vii-methyljuglone from the root and a series of its derivatives on MCF-seven, HeLa, SNO, and DU 145 human being cancer jail cell lines had IC50 values ranging from v.three to 10.1μM [135]
Kigelia africana Lam. Benth.
Lapachol, 3-(2′- hydroxyethyl)-5-(2″-hydroxypropyl) dihydrofuran-2-(3H)ane, specioside, verminoside, and minecoside, kigelin, β-sitosterol, ane,three-dimethylkigelin, and ferulic acid
Seed oil suppressed human colon adenocarcinoma (Caco-two) and homo embryonic kidney (HEK-293) cell growth in a dose-dependent manner [140]
An 80% methanol extract of the roots exhibited cytotoxicity to brine shrimps with LCfifty of 7.2μk/ml [138]
Fruit extracts increased the sub-G1 phase (apoptosis) population in HCT116 human colon cancer cells [141]
Markhamia lutea (Benth.) K. Schum
Cycloartane triterpenoids, musambins A–C and their 3-Oxyloside derivatives musambiosides A–C [142], Oleanolic acid, pomolic acid, 2-epi-tormentic acid, musambin A, and b-sitosterol-three-O-b-D-glucopyranoside [143, 144]
Anticancer action against Ehrlich ascites carcinoma cells with an ICl value of 27.0μg/mL [143]. Cytotoxicity against KB (mouth epidermoid carcinoma) and the human diploid embryonic lung cells (MRC5) though nigh IC50 values were >fiftyμgrand/mL [144]
Cytotoxic confronting colon cancer (Colo-320 DM), breast cancer (MCF-7), ovary cancer (PA-1), and oral cancer (KB-403) cell lines with ICxc value of 3.98, 17.lx,12.86, and 8.fortyμthousand/mL, respectively [145]. Methanol extracts were cytotoxic to man B-lymphocyte plasmacytoma (U266B1) cell line with ICfifty of 0.32μg/ml [147]. Aqueous foliage extract acquired a dose-dependent subtract in HeLa cell viability with ICfifty of 70μg/mL [148]. Leaf extracts displayed pregnant antiproliferative activity ( ) against human being liver (hepatocellular carcinoma, Hep-G2) and muscular (rhabdomyosarcoma, RD) jail cell lines [149]. The ICl of leafage extracts cytotoxicity on cisplatin-resistant ovarian cancer (A2780CP20) and prostate cancer (PC3) cell lines in a study was 0.27 and 0.17 mg/mL, respectively [150]
Apoptosis analysis performed using leaf and bark extracts on breast and colorectal cancer lines showed a remarkable increment in the number of apoptotic cells with a sevenfold increase in breast (MD-MB-231) cell line to an increase of several folds in colorectal cancer (HCT-8) prison cell line [146]
Leaf extracts inhibited the growth of hepatocarcinoma (HepG2), colorectal adenocarcinoma (Caco-2), and breast adenocarcinoma (MCF-7) cell lines with dichloromethane leaf extract having IC50 betwixt 112 and 133μg/ml [151]. Leaf extracts caused the decease of 72–82% of acute myeloid leukemia cells and 77–86% of acute lymphoblastic leukemia cells after 24 hours of incubation with xxμg/ml of the extract. At the same time, 69–81% of HepG2 cells died after handling with ethanol extract [152]. Foliage extracts also showed in vitro anticancer activity on homo hepatocellular carcinoma (HepG2) cells. At a maximum dose of 200 mg/kg, the survival of HepG2 and non-small-cell lung cancer (A549) cells was reported to decrease past lx% and 50%, respectively [153]
Leaf extract had anticancer activity against human epidermoid cancer (Hep2) cell line with IC50 of 12.vμg/mL in the well-nigh active fraction [154]. Cytotoxicity of h2o-soluble leaf extract was reported against human alveolar epithelial cells derived from the lung cancer (A549) cell line with IC50 of 166.7μone thousand/mL [155]
Jail cell viability of leaf extract-treated A549, HepG2, CaCo2, Hek293, and Jurkat cells was reported to be reduced with ICfifty from 0.05 to 0.4% [156]
Human pancreatic cancer cells (Panc-1, p34, and COLO-357) were inhibited by leaf extracts with IC50 of one.1, i.5, and 1.8 mg/mL [157]
Seed extracts had cytotoxic potential against A549, Hep-ii, HT-29, and IMR-32 cancer cell lines [158]. β-sitosterol-3-oglucopyranoside, 4-(α-L-rhamnosyloxy) benzyl isothiocyanate, and niazimicin prevented the induction of Epstein–Barr virus genome in Raji cells. Niazimicin delayed the formation of tumors and reduced the number of tumors in vivo [159]
Opuntia species
Quercetin, kaempferol-3-O-rutinoside, isorhamnetin-3-O-rutinoside, betanin, and indicaxanthin [160]
Fruits, peels, seed, cladode, stalk, and root extracts of dissimilar species take cytotoxicity confronting mammary (MCF-7), prostate (PC3), colon (Caco2, SW-480, HT-29), HeLa cervical carcinoma, myeloid leukemia (K562), and hepatic (HepG2) prison cell lines [161–164]
Oxalis corniculata Linn.
Palmitic, 8 oleic, linoleic, linolenic, stearic, tartaric, and citric acids, flavones (acacetin and 7,4′-diOMe apigenin), glycoflavones (4′-OMe vitexin, 4′-OMeiso-vitexin and three′,four′-diOMe orientin), flavonols (3′,4′-diOMe quercetin), and phenolic acids such as p-hydroxybenzoic, vanillic, and syringic acids [165]
The ethanolic extract inhibited tumor growth of Ehrlich ascites carcinoma (EAC) induced in Swiss albino mice [166]
Prunus africana (Hook.f.) Kalkman
Ursolic acid, oleanolic acid, β-amyrin, atraric acid, Due north-butylbenzene-sulfonamide, β-sitosterol, β-sitosterol-3-O-glucoside, ferulic acid, and lauric acid [167–169]
Antiprostate cancer activeness targets fast dividing cells past impairing mitosis or by causing target cells to undergo apoptosis [169, 170]. There was growth inhibition of a human prostate cancer cell line (PC-3) and epithelial cells derived from a lymph-node carcinoma of the prostate (LNCaP) by l% at ii.5μFifty/mL and also induced significant apoptosis in both cell lines (PC-3 and LNCaP) at ii.5μL/mL compared to untreated cells. The ethanolic extract had an antimitogenic issue on prostate cancer cells past inhibiting the mitogenic action of epidermal growth factor which resulted in a decreased number of cells entering the S-phase of the cell cycle [171]
Zanthoxylum chalybeum Engl.
Skimmianine, furoquinoline alkaloid skimmianine, the benzophenanthridine alkaloids chelerythrine and nitidine, the aporphine alkaloids tembetarine, magnoflorine, N-methylcorydine, North-methylisocorydine (menisperine), and berberine and the phenylethylamine candicine, alkamide, fagaramide, dihydrochelerythrine, lupeol, and sesamin [172]
Extracts showed moderate cytotoxicity with ICl values beneath 50μM confronting the drug-sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cell lines [172]
Stem bark extracts exhibited potential cytotoxicity effect with LC50 value of five.74μg/mL in brine shrimp analysis [173]
Cytotoxicity reported confronting man cancer cell line HL-60 cells with IC50 of 137.31μthou/mL and selectivity index of 3.81 [174]. Cytotoxicity against human gingival fibroblasts cells with IC50 of 26 ± 3μthousand/mL [175]
Cytotoxicity of root bark extracts reported with ICl of 38.5, 68.nine and < 500μg/mL in brine shrimp toxicity assay [97, 134, 176]
IC50: -median inhibitory concentration/half maximal inhibitory concentration, LC50: median lethal concentration, and IC90: concentration inhibiting 90% of cellular growth.
(a)
(b)
Plant
Ethnomedicinal uses
Biological activities
Abelmoschus esculentus (Fifty.) Moench
Treatment of syphilis, immunity boosting and treatment of anaemia, cuts, wounds, boils, catarrhal infections, ardor urinae, dysuria, and gonorrhoea [177]
Immunomodulating, antioxidant, antidiabetic, and antihyperlipidemic activities [178]
Albizia coriaria (Welw. Ex Oliver)
Treatment of center diseases, meat allergy, nausea, headaches, mental illness, diarrhea, cough, tuberculosis, anaemia, syphilis, postpartum haemorrhage, snakebites, sore throats, herpes zoster, menorrhagia, stimulating milk production in lactating mothers, threatened ballgame, skin diseases, jaundice, cough, steam fumigation treatments for sore eyes, and as a general tonic [33, 142, 179]
Antibacterial activity [58]
Allium sativum L.
Arteriosclerosis, management of diabetes mellitus, asthma, deafness, leprosy, bronchial congestion, fevers, worms, and liver gall bladder trouble [180]
Antidiabetic, hepatoprotective, antimicrobial, and antihyperlipidemic activities [181]
Annona muricata L.
Leaves are used to treat cystitis, diabetes, headaches, colds, influenza, asthma, and insomnia [182]
Antiviral, antinociceptive, anti-inflammatory, and antihyperglycemic activities [183]
Artemisia annua 50.
Treatment of cough, indigestion, malaria, fever caused by tuberculosis, and jaundice [33]
Antimalarial, antimicrobial, and anti-inflammatory activities [184]
Beta vulgaris 50.
Management of hypertension, purifying blood and liver, and reducing inflammation [32]
Antioxidant and antibacterial activities [94]
Blighia unijugata Baker
Treating fibroids [43], airsickness, malaria, and skin diseases [185]
Antiplasmodial, antimalarial, and antioxidant activities [186]
Opuntia species
Handling of peel wounds, tum swelling, digestive problems, type 2 diabetes, colitis, high cholesterol, urinary tract infections, weight loss aid to treat obesity and overweight, and as a remedy for booze hangovers [40, 41, 187]
Antidiabetic, antimicrobial, antioxidant, and anti-inflammatory activities [188]
Cannabis sativa L.
Treatment of coughing, tuberculosis, cancer pain, asthma and diarrhea [33], appetite stimulant in debilitating diseases, attenuation of wasting [189], antiemetics, treatment of multiple sclerosis, spinal cord injuries, Tourette'due south syndrome, epilepsy, and glaucoma [190]
Anti-inflammatory and antinociceptive activities [191]
Canarium schweinfurthii Engl.
Management of anaemia [39], dysentery, coughs, chest pains, tuberculosis, stomach complaints, food poisoning, purgative and emetic, roundworm infections and other intestinal parasites. Used as an emollient, stimulant, diuretic and in treatment of skin infections, eczema, leprosy, ulcers, diabetes mellitus, colic, tummy pains, pains after childbirth, gale, inappetence, fever, constipation, malaria, sexually transmitted infection, and rheumatism [33, 192, 193]
Antioxidant, analgesic, antibacterial, anti-inflammatory, and antidiabetic activities [194, 195]
Carica papaya L.
Treatment of cough, diarrhea, snake seize with teeth, sterility, pain killer, antidotes, promotes labour, cracks on soles of feet, low amnesty, loss of memory, measles, erectile dysfunction [42, 43], and fevers [196], leaves used as an antipyretic, for malaria, splenomegaly, and HIV handling [33, 185, 197, 198]. Fruit used to manage anaemia, worms, asthma, and tonsillitis [199]. Root extracts with that of Carissa edulis and Euclea divinorum used for treatment of venereal diseases [200]
Antibacterial, antimalarial, antifungal, and immunomodulatory activities [106, 107, 201]
Capsicum frutescens L.
Direction of hernia, pancreas disorders, erectile dysfunction (roots) [43]. Used with Clematis hirsuta Perr. & Guill. for treating influenza and mental issues [202], headache, and indigestion [199]. Equally a salve to relieve muscle, joint, and toothache hurting, to care for cough, asthma, and sore throat, every bit a stimulant, and to care for stomachache, seasickness, and flatulence [203]
Handling of athletes pes, wounds, hypertension, diabetes and hormonal imbalance [43], stomachache and migraine [44], excessive menstruation, cough, and antidote to poisoning [199]
Antifungal and antioxidative activities [223]
Prunus africana (Hook.f.) Kalkman
Used for managing fainting [43], malaria, HIV, coughing, chest pain, epilepsy, heart diseases, diarrhea [33, 198], urinary tract infections, pregnancy [44], fever, and inappetence [102]
Anti-inflammatory, antioxidant, and antimalarial activities [215, 224]
Vitex fischeri Gürke
Treatment of canker zoster, peel infections, rashes, tuberculosis [33]
Anticandidal activity [211, 225]
Zanthoxylum chalybeum Engl.
Treatment of stomachache, cough, fever, pare rush, diabetes [33, 42, 43], HIV [198], malaria, diarrhea, sickle cell, tuberculosis, pneumonia, colds, ulcers, sore throat, measles, bilharzia, amoebiasis, female sterility, uterine fibroids, and headache [226–230]
Anticandidal, antibacterial, and antidiabetic activities [173, 231–233]
NR: none retrieved in the open up literature.
3.1. Traditional Concept of Cancer in Uganda
From the electronic survey, it is articulate that local communities in Uganda have some data virtually cancer. Not all Ugandans are fully enlightened of cancer considering about information on it is disseminated through television and radio stations which not all have access to. Another hitting challenge is that there is no word for cancer in any of the Ugandan local languages. Thus, many ignore cancer considering it is not anywhere recited equally a health problem in their local vocabulary [16]. To many, being diagnosed with any type of cancer is equated to receiving a death judgement [234]. Some believe that conventional treatments usually cause cancer to spread, fastening the death of victims [16]. In addition, due to the ever-irresolute landscape of bachelor handling options, nearly patients believe that cancer can only be cured using herbal medicine and the all-time mode to bargain with cancers is through prevention [23]. Many Ugandans presume that herbal products are safer to use than allopathic drugs. In Northern Uganda, the apply of shea (Vitellaria nilotica) butter, simsim (Sesame indicum 50.), and groundnut (Arachis hypogea Fifty.) pastes equally substitutes for refined cooking oil and vaseline with the belief that the latter are carcinogenic is known. Unfortunately, recent reports have pointed out that some of these food items are contaminated with mycotoxins, particularly aflatoxins which are potential carcinogens [19, 235].
3.2. Anticancer Plants Used in Local Communities of Uganda
Cancer chemoprevention which involves the inhibition or reversion of cancer through the administration of natural or synthetic agents has gained a wider audition in Uganda. Chemopreventive agents may inhibit cancer evolution either by limiting exposure to carcinogens (carcinogen germination inhibitors and blocking agents) or by decreasing tumor promotion or progression stages (suppressing agents) [236]. Many compounds from medicinal or dietary plants have been reported equally chemopreventive agents capable of inhibiting DNA damage and retarding or reversing carcinogenesis in in vitro and in vivo bioassays [237].
From our survey, 29 institute species from 28 genera belonging to 24 botanical families claimed as anticancer plants in Republic of uganda have been reported (Table 1). The nearly cited families were Bignoniaceae (vii%), Caricaceae (7%), Fabaceae (7%), Moraceae (seven%), and Rutaceae (7%). Most families encountered in this written report have reported use in the traditional direction of cancer in other countries across the globe. For case, Apocynaceae, Asteraceae, Bignoniaceae, Caricaceae, Fabaceae, Malvaceae, Meliaceae, Moraceae, Rutaceae, Sapindaceae, and Solanaceae were cited in Republic of kenya [170], Ethiopia [238], Tanzania [97], and Almost E (Arabian Peninsula, Egypt, Iraq, Iran, Israel, Hashemite kingdom of jordan, Lebanese republic, Palestinian territories, Syria, and Turkey) [239], Lamiaceae in Kingdom of morocco [240], and Apocynaceae, Meliaceae, and Malvaceae in Sri Lanka [241].
In addition, some of the institute species recapitulated take been documented in the treatment of cancer globally; for instance; Carica papaya 50., Catharanthus roseus (L.) Chiliad. Don, and Prunus africana (Hook.f.) Kalkman were reported to be used for traditional treatment of cervical, colorectal, prostate, and breast cancers [114, 170, 242] while Albizia coriaria Welw. ex Oliver, Capsicum frutescens Fifty., and Kigelia africana (Lam.) Benth. has been reported for the treatment of squamous prison cell carcinoma, pharynx, and breast cancers in Republic of kenya [170]. Zanthoxylum chalybeum Engl. is used in Federal democratic republic of ethiopia and Tanzania for the treatment of breast and cervical cancers [97, 243], Blighia unijugata Baker is used for the treatment of chest and cervical cancers in Tanzania [97], while Cymbopogon citratus (DC.) Stapf is used against colorectal cancer in Kenya [170]. Interestingly, some of these plants are consumed equally food spices; for instance, Cymbopogon citratus (DC.) Stapf is used by nearly communities in Northern Uganda who cannot afford tea (Camellia sinensis (50.) Kuntze) leaves, and Beta vulgaris L. and Daucus carota L. are mutual ingredients in Ugandan culinary recipes [93]. Indeed, epidemiological studies have supported that dietary intake of fruits, vegetables, and teas tends to lower the run a risk of man cancers [244].
Farther, some of the botanical species have been reported every bit recipes of anticancer preparations in other countries. For case, P. africana stalk bark is used in combination with Harungana madagascariensis Lam. ex Poir, Zanthoxylum gilletii (De Wild.) P.G. Waterman (stem bawl), Spathodea campanulata P. Beauv, and Vernonia lasiopus O. Hoffman (stem bawl), and P. africana (stem bark and roots), Aloe volkensii leaves, Spathodea campanulata P. Beauv (leaves and stalk bark), and Harungana madagascariensis Lam. ex Poir (stem bark) boiled with Trichilia emetica Vahl. are used for the treatment of skin, breast, and colorectal cancers in Republic of kenya [170]. Similarly, Markhamia lutea (Benth.) K. Schum stem bawl lonely or in combination with Albizia gummifera stem bawl and Conyza sumatrensis (Retz.) E.H Walker leaves is used in the management of squamous cell carcinoma of the gums, colorectal, throat, and breast cancers in Kenya [170]. In Tanzania, Kigelia africana (Lam) Benth. stalk bark mixed with approximately equal weights of root barks of Maclura africana (Bureau) corner, Harrisonia abyssinica Oliv., and Warburgia stuhlmannii Engl. is drunk for the treatment of chest, liver, and colon cancers [97]. Euclea natalensis A. DC. root bark boiled with the root barks of Harrisonia abyssinica is drunk equally a treatment for leukemia in Tanzania [97].
Some of the plants accept been reported to accept cytotoxic and antitumor properties (Table 2) and many possess other ethnomedical applications (Table three) both in Uganda and internationally. Interestingly, the isolation, characterization, and purification of the anticancer and cytotoxic phytoconstituents take been successfully done in some species (Figure 1). Hit examples are Prunus africana (Hook.f.) Kalkman which have been patented in France for the management of prostate cancer [245] and Catharanthus roseus (50.) G. Don from which the commercial anticancer drugs vincristine and vinblastine have been developed [246].
Phytochemicals from plants are reported to be effective confronting cancer cells because they have many molecular targets [247]. For example, -sitosterol nowadays in P. africana has been shown to showroom anti-inflammatory, antineoplastic, and immunomodulating activities [248]. It is worth mentioning that antioxidant activities and antitumor or anticancer properties of establish extracts are always reported concomitantly in several plants [166], and some studies demonstrated that there is a positive linear relationship between antioxidant activity and anticancer effect of plant extracts [249]. Plant phytochemicals such every bit artemisinin from the Artemisia genus are reported to have an endoperoxide moiety which is strategic for their bioactivity. The cleavage of this is reported to produce reactive oxygen species, inducing oxidative stress. Furthermore, in the presence of ferrous fe or reduced heme, artemisinin can convert itself into cytotoxic carbon-centred radical, a highly potent alkylating agent, to induce directly oxidative damage to cancer cells [250, 251]. Thus, they are reported to induce apoptosis and ferroptosis, reduce prison cell proliferation through cell wheel abort, and inhibit angiogenesis and tissue invasion of the tumor too as cancer metastasis [184, 250, 251].
3.3. Growth Habit, Parts Used, Preparation, and Style of Administration
Most anticancer plant species reported in Uganda occur in the wild (52%) though some are cultivated (48%). The growth habit of the plants is as trees (55%) or herbs (45%). Anticancer extracts are usually prepared from leaves (29%), bark (24%), roots (21%), fruits (13%), seeds (v%), bulb (5%), or rhizomes (3%). The regular utilise of roots and leaves in traditional medicine is a feature feature of materia medica in Uganda [26]. Equally reported elsewhere [238, 240], embryonal establish parts such every bit fruits, seeds, buds, bulbs, and flowers which are reported to accrue bioactive compounds are less frequently used in anticancer therapy in Uganda.
Usually, anticancer preparations are presented as decoctions and teas (53%) and spices eaten in nutrient (23%) or pounded to produce ointments that are applied topically (10%). The plants are collected from the wild, cultivated fields, or dwelling gardens when needed. Traditional medicine practitioners either collect herbal plants personally or hire collectors. All traditional medical practitioners cultivate some medicinal plants especially fast growing ones around their homes and shrines in order to have them inside easy access when needed [26]. The preparations are majorly administered orally, except in cases of skin cancers where they are applied topically every bit ointments.
3.four. Other Ethnomedicinal Uses and Toxicity of the Reported Anticancer Plants
Almost all the plants recapitulated in this review are employed for the handling of various ailments other than cancer. Albizia coriaria (Welw. ex) Oliver used in the direction of venereal diseases (syphilis, HIV, and gonorrhoea), postpartum haemorrhage, sore throats, menorrhagia, threatened abortion, pare diseases, jaundice, cough, and sore eyes [33, 179] is a good representative instance. Such plants tend to be used in unlike communities for treating cancer and tin exist a good justification for their pharmacological efficacy [26].
On the other hand, some of the anticancer plants cited exhibit marked toxicity. A striking example is Catharanthus roseus (Fifty.) G. Don. The alkaloids in information technology are neurotoxic, especially vincristine [252]. Vincristine and vinblastine are highly toxic antimitotics, blocking mitosis in metaphase after binding to the microtubules [253]. Evidently, side furnishings such as myelosuppression, alopecia, abdominal cramps, constipation, nausea, paralytic ileus, ulcerations of the rima oris, hepatocellular damage, kidney impairment, pulmonary fibrosis, urinary retention, amenorrhoea, azoospermia, orthostatic hypotension, and hypertension [254–256] accept been reported for the commercial drugs vincristine and vinblastine derived from this plant. In essence, the administration of these drugs must be advisedly controlled to reduce the side effects [257]. This observation explains, in part, why some anticancer preparations in Uganda are practical topically or ingested in small amounts. Fortuitously, topical application is a better arroyo for reducing the local activity of cancer cells at externally affected parts.
three.5. Clinical Studies
At present, clinical trials utilizing standardized extracts of anticancer plants reported in Uganda or their bioactive compounds have not been done with the exception of Prunus africana (Hook.f.) Kalkman and Catharanthus roseus (L.) Yard. Don. which have been investigated in other countries [245, 246]. Prostafx, Tadenan, and Pygenil are some of the herbal preparations of Prunus africana (Hook.f.) Kalkman on the market. Due to the paucity of data generated from preclinical tests (pharmacokinetic and toxicological studies) and the regulatory requirements for clinical studies, the safety and efficacy of traditional anticancer establish preparations used in Uganda remain a underground nevertheless to be unveiled. Although there are many research institutes such every bit Uganda Virus Research Institute, Natural Chemotherapeutic Research Establish, Uganda Industrial Research Institute, and National Agricultural Research Institute, none is designed to take an in-depth focus on drug discovery and development to the level of commercialization. Thus, the authorities of Uganda should found an institute that handles drug discovery and evolution to enhance the utilization of medicinal plants in Uganda.
4. Conclusions and Recommendations
The inventory of plants utilized by Ugandan communities presents considerable potential for the treatment of cancer. Cyperus alatus (Nees) F. Muell, Ficus dawei Hutch, Ficus natalensis Hochst, and Lovoa trichilioides Harms are some of the plants with claimed anticancer potential that have been hardly studied and therefore warrant further investigations. More ethnobotanical surveys should be done in the unsurveyed districts to identify other potential anticancer plants. Albizia coriaria Welw. ex Oliver which doubles equally an antivenin institute will be investigated for its anticancer potential in a penultimate report.
Disclosure
Timothy Omara and Sarah Kagoya are co-first authors.
Conflicts of Involvement
The authors declare that at that place are no conflicts of involvement regarding the publication of this paper.
Timothy Omara and Sarah Kagoya contributed equally.
Acknowledgments
TO, DMN, PN, LNK, AJ, AM, BJK, IM, CKN, and MKC are grateful to the Earth Bank and the Inter-University Quango of Due east Africa for the scholarship awarded to them through the Africa Centre of Excellence Ii in Phytochemicals, Textiles, and Renewable Energy (ACE II PTRE) hosted at Moi Academy that prompted this concerted ethnomedical communication. The authors commend preceding authors for their useful quest for knowledge on medicinal plants in Uganda, the reports of which this study was based.
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