More plants for cancer treatment validated

The search for more plants that could be used to treat cancers has intensified and is yielding positive results.A study published in International Research Journal of Biochemistry and Bioinformatics has validated anti-cancer properties of some plants used in traditional medicine in Nigeria.

The plants, according to the researchers led by Taye T. Alawode from the Department of Chemical Sciences, Federal University Otuoke, Bayelsa State, include:Allium ascalonicum (Shallot, Spring Onion)

Mohammadi-Motlagh H. et. al (2011) evaluated the effects of the aqueous extract of A. ascalonicum on viability of the three cancer cell lines including K562, Wehi164 and Jurkat, and normal cell line (HUVEC) using Trypan blue and LDH assays evaluation.

On the basis of obtained results, after 24, 48 and 72 hours of incubation, the extract significantly reduced the viability of three cell lines at different concentrations compared with the control group, and these effects were stronger as time increased. The cytotoxic effects of A. ascalonicum for Wehi164 cell line were considerably lower than those on K562 and Jurkat cell lines. Treatment of HUVECs as normal cell lines with the aqueous extract of the A. ascalonicum bulbs up to 1000 μg/ml or even higher concentrations for 72 hours showed no considerable cytotoxic effect on the HUVECs.

At 1000 μg/ml, there was no significant difference in viability between the test and control wells. The Coulter counter determined the antiproliferative activity of the A. ascalonicum extract on the cancer cell lines. After treatment with 25-200 μg/ml and higher concentrations of the extract for 72 hours, the proliferation ratio of K562 and Jurkat cell lines decreased gradually as compared with controls.

However, the extract could not inhibit the proliferation of Wehi164 cell line significantly at similar concentrations, unless they are higher than 400 μg/ml. These results showed that A. ascalonicum inhibited the proliferation of all cell lines in a dose-dependent manner. K562 and Jurkat cells showed the highest susceptibility (GI50: 100μg/ml), and Wehi164 cells displayed the lowest susceptibility to A. ascalonicum with GI50 at 400μg/ml.

Allium cepa (Onion)
Ethanol (95 per cent) extract of onion, administered to cats and rats at dose of 50mg/kg, produced weak activity on Sarcoma III (MKT). Essential oil applied externally on female mice at a dose of 1mg/animal has been reported to be effective against carcinoma induced by twice weekly 12-O tetradecanoyl-phorbol-13-acetate promotion for two weeks, followed by mezerein promotion for 18 weeks (Fulda, 2008 cited in Nath, 2010). The dose, when given with a second promoter, produced a 32 per cent decrease in incidence of papiloma in 7,12-dimethylbenz[α]anthracene(DMBA)-induced carcinogenesis. Hot water extract of fresh bulb applied externally on mice was active against DMBA-induced carcinogenesis.

Epidemiological data both support and refute, the concept that higher intake of onions is positively related to lower risk for carcinoma. It has been noted that persons in the highest consumption category versus the lowest has a 50 per cent reduced risk of cancers of the stomach, alimentary and respiratory tracts. Onion is one of the richest sources of organosulphur compounds. Organosulphur compounds such as diallyldisulphide, S-allylcysteine and S-methylcysteine have been shown to inhibit colon and renal carcinogenesis.

Also, Nigerian researchers led by a professor of pharmacognosy at the University of Nigeria Nsukka (UNN), Chief Executive Officer of Bioresources Development Group (BDG), and former Chairman of the Independent Election Commission (INEC), Prof. Maurice Iwu, have validated local foods such as bitter kola (Garcinia kola), coconut oil, Zobo (Hibiscus sabdariffa), bitter leaf (Vernonia amygdalina), Moringa oleifera, tomato, Sour sop, African bush mango (Ogbono), among others as medicines.

Iwu told journalists that his team has developed dietary supplements based on these local foods for managing chronic diseases like diabetes, hypertension, prostate cancer, erectile dysfunction, Human Immuno-deficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS), among others. Iwu told journalists in Lagos last week that his team at BDG has formulated local food items into scientifically validated medicines, dietary supplements.

BDG is comprised of Bioresources Development and Conservation Programme, Bioresources Institute of Nigeria, Intercedd Health Products (IHP), Intercedd Laboratories (IL), BioTrade Global Agency and Nature’s Emporium.

The foods that can be used as medicines or rather dietary supplements include among others: Moringa Tea, Moringa Leaf Tea, Moringa Whole Seed, which have been shown by research to cure over 300 diseases; Bissap Tea from Zobo (Hibiscus sabdariffa) for hypertension; Vernonia Ocimum Tea from bitter leaf (Vernonia amygdalina) and scent leaf (Ocimum gratissimum) for control of blood sugar and weight management; Garcinia-IHP from bitter kola (Garcinia kola) and used as antimicrobial and detoxifier; IHP Virgin Coconut Oil from coconut as stress buster and immune booster; Erovit-IHP, which combines the anti-ageing properties of the mushroom, Cordyceps, the high-potency antioxidant effects of Punica granatum fruits and the life enhancing Korean ginseng; and Immunovit-IHP from Reishi mushroom, Punica granatum and Korean ginseng to boost immunity against diseases.

Iwu said the products have been validated by the United States Food and Drug Administration (FDA); the National Agency for Food Drug Administration and Control (NAFDAC); the Nigerian Institute of Pharmaceutical Research and Development (NIPRD), Abuja; the Nigerian Export Promotion Council; the Raw Material Council; and the Federal Institute of Industrial Research (FIIRO), Lagos, for prevention and management chronic diseases.

Allium sativum (Garlic)
The bulb is used in ethnomedicine to treat fever, coughs, asthma, dilated bronchi, and flatulence, as an anthelmintic, antibiotic, diuretic, antimicrobials, blood tonic, and emmenagogue. When garlic oil was topically applied during the initiation phase of benzo (a) pyrene (BP) induced carcinogenesis in mice, a decline was noted in the incidence and multiplicity of tumours. Oral administration of fresh water extract of garlic was shown to result in reduction of chemically induced cervical carcinomas in mice. Garlic treatment inhibited development of murine transitional cell carcinomas significantly. Sengupta et. al (2002) observed that fresh garlic juice administered orally can prevent development of azoxymethane (AOM) induced aberrant crypt foci and adenocarcinoma in rat colon.

Epidemiologic and laboratory studies suggest that allium vegetables and garlic constituents have antitumor effects. Garlic contains several potentially important agents that possess antitumor and anticarcinogenic properties. Several compounds are involved in garlics possible anticancer effects. Garlic contains allyl sulphur and other compounds that slow or prevent the growth of tumor cells. Many have investigated the efficacy of various garlic-derived compounds in inhibiting experimental carcinogenesis. It was demonstrated that diallylsulfide (DAS), diallyltrisulphide (DAT), allylmethyldisulphide (AMD) and allylmethyltrisulphide (AMT) inhibit gastric malignancy induced by BP in mice.

Fukushima et al. (1997) analysed the potential of several organosulphur compounds present in garlic and onion and observed inhibitory effect of DAS on renal and colon carcinogenesis in rat induced by diethylnitrosamine (DEN).

Bryophyllum pinnata (Resurrection plant, Life plant, Never-die plant)
Mahata et al. in 2012 characterized chloroform fractions of B. pinnata for phytochemical compounds by TLC, HPTLC and NMR and biological activity of the fractions were examined based by MTT-based cell viability assay, Electrophoretic Mobility Shift Assay, Northern blotting and assay of apoptosis related proteins by immune-blotting in human cervical cancer cells.

The results showed presence of growth inhibitory activity in the crude leaf extracts with IC50 at 552μg/ml, which resolved to fraction F4 (Petroleum Ether: Ethylacetate 50:50) and showed IC50 at 91μg/ml. Investigations of anti-viral activity of the extract and its fraction revealed a specific anti-HPV activity on cervical cancer cells as evidenced by down-regulation of constitutively active AP1 specific DNA binding activity and suppression of oncogenic c-Fos and c-Jun expression, which was accompanied by inhibition of HPV18 transcription. In addition to inhibiting growth, fraction F4 strongly induced apoptosis as evidenced by an increased expression of the pro-apoptotic protein Bax, suppression of the anti-apoptotic molecules Bcl-2, and activation of caspase-3 and cleavage of PARP-1.

Phytochemical analysis of fraction F4 by HPTLC and NMR indicated presence of activity that resembled Bryophyllin A. The study demonstrates presence of anticancer and anti-HPV activity in B. pinnata leaves that can be further exploited as potential anticancer, anti-HPV therapeutic for treatment of HPV infection and cervical cancer.

Vernonia amygdalina (Bitter leaf)
Yedjou et. Al (2008) assessed the therapeutic efficacy of Vernonia amygdalina (VA) leaf extracts as anti-cancer agent against human breast cancer in vitro using the MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and alkaline single cell gel electrophoresis (Comet) assays, respectively. In this experiment, human breast adenocarcinoma (MCF-7) cells were treated with different doses of VA leaf extracts for 48 hours.

Data obtained from the MTT assay showed that VA significantly ((P < 0.05) reduced the viability of MCF-7 cells in a dose-dependent manner upon 48 hours of exposure. Data generated from the comet assay also indicated a slight dose-dependent increase in DNA damage in MCF-7 cells associated with VA treatment. A slight increase in comet tail-length, tail arm and tail moment, as well as in percentages of DNA cleavage at all doses tested, showed an evidence that VA-induced minimal genotoxic damage in MCF-7 cells. Taken together, this suggests that VA treatment moderately (P < 0.05) reduces cellular viability and induces minimal DNA damage in MCF-7 cells. These findings provide evidence that VA extracts represent a DNA-damaging anti-cancer agent against breast cancer and its mechanisms of action functions, at least in part, through minimal DNA damage and moderate toxicity in tumors cells.

Annona muricata (Soursop)
Hamizah et. Al (2012) evaluated the chemopreventive effects of ethanolic extracts of leaves of A. muricata (AMLE) in six to seven week old ICR mouse given a single topical application of 7,1 2-dimethylbenza (α) anthracene (DMBA 100μg/100μl acetone) and promotion by repeated application of croton oil (1 per cent in acetone/twice a week) for 10 weeks.

Morphological tumor incidence burden and volume were measured, with histological evaluation of skin tissue. Topical application of AMLE at 30, 100 and 300mg/kg significantly reduced DMBA/croton oil induced mice skin papilloma genesis in (i) peri-initiation protocol (AMLE from seven days prior to days after DMBA), (ii) promotion protocol (AMLE 30 minutes after croton oil), or (iii) both peri-initiation and promotion protocol (AMLE seven days prior to seven day after DMBA and AMLE 30 minutes after croton oil throughout the experimental period), in a dose dependent manner (p<0.05) as compared to carcinogen–treated control. Furthermore, the average latent period was significantly increased in the AMLE-treated group.
Interestingly, at 100 and 300-mg/ kg, AMLE completely inhibited the tumor development in all stages.

Histopathological study revealed that tumor growth from the AMLE-treated groups showed only slight hyperplasia and absence of keratin pearls and rete ridges. The results, thus suggest that the

A. muricata leaves extract was able to suppress tumor initiation as well as tumor promotion even at lower dosage. Rachmani et. al (2012) determined the cytotoxic effects of extracts of leaves of A. muricata and its fractions in cancer cells T47D.

Extraction was carried out with ethanol and fractionation by column chromatography method, n-hexane, chloroform, ethylacetate and methanol were used. Cytotoxicity was determined using MTT assay and apoptosis tests were performed by Double Staining method.

The results showed that ethanol extracts has an IC50 value of 17.149μg/mL. Fraction F3 has the best cytotoxic activity with IC50 value of 30.112μg/mL. Apoptosis assay results showed that the fraction F3 was able to induce apoptosis of cells.

Kigelia Africana (Sausage tree)
The root bark is recommended for the treatment of cancer of the uterus. The extract has been tested against melanoma cells (a tumour of pigmented skin cells, which can develop into malignant melanoma-the potentially fatal form of skin cancer). The extract inhibited the growth of cultured melanoma cells to a significant degree. The extract of stem bark and fruit are reported for their cytotoxic activities and showed promising results in treating melanoma and renal carcinoma.

Mangifera indica (Mango tree)
Noratto et al. (2010) compared the anticancer properties of polyphenolic extracts from several mango varieties (Francis, Kent, Ataulfo, Tommy Atkins and Hadin) in cancer lines, including Molt-4 leukemia, A-549 lung, MDA-MB-231 breast, LnCap prostate, and SW-480 colon cancer cells and non-cancer colon cell line CCD-18Co.

The efficacy of extracts from all mango varieties in the inhibition of cell growth was tested in SW-480 colon carcinoma cells, where Ataulfo and Haden demonstrated superior efficacy, followed by Kent, Francis, and Tommy Atkins. At 5 mg of GAE/L, Ataulfo inhibited the growth of colon SW-480 cancer cells by approximately 72 per cent.

while the growth of noncancerous colonic myofibroblast CCD-18Co cells was not inhibited. The growth inhibition exerted by Ataulfo and Haden polyphenols in SW-480 was associated with an increased mRNA expression of pro-apoptotic biomarkers and cell cycle regulators, cell cycle arrest, and a decrease in the generation of reactive oxygen species. Overall, polyphenols from several mango varieties exerted anticancer effects, where compounds from Haden and Ataulfo mango varieties possessed superior chemo preventive activity.

Percival S. et al. screened whole mango juice and juice extracts for antioxidant and anticancer activity. They measured anticancer activity by examining the effect on cell cycle kinetics and the ability to inhibit chemically induced neoplastic transformation of mammalian cell lines. Incubation of HL-60 cells with whole mango juice and mango juice fractions resulted in an inhibition of the cell cycle in the G0/G1 phase. A fraction of the eluted mango juice with low proxy radical scavenging ability was most effective in arresting cells in the G0/G1 phase.

Whole mango juice was effective in reducing the number of transformed foci in the neoplastic transformation assay in a dose-dependent manner. The chemo preventive effects of mangiferin for both the initiation and post-initiation phases of azoxymethane (AOM; alkylant, 15 mg/kg body weight, s.c. once a week for three weeks) – induced colon carcinogenesis were examined in rats by Yoshimi et al. (2001).

In a short-term assay (five weeks, development of AOM-induced preneoplastic lesions), mangiferin (0.1 per cent in the basal diet for five weeks) significantly inhibited the aberrant crypt foci development in AOM-treated rats (~40 per cent less).In a long-term assay (40 weeks), the group treated with mangiferin during the AOM initiation phase had significantly lower and multiplicity of intestinal neoplasms (greater than 40 per cent reduction) with reduced colonic mucosa cell proliferation (65 to 85 per cent decrease).