Comparative inhibition of MCF-7 breast cancer cell growth, invasion and angiogenesis by Cannabis sativa L. sourced from sixteen different geographic locations

Molecular mechanism of Cannabis sativa L. on some of its claimed possible health benefits have not been thoroughly explored despite the global commercialization of Cannabis products. The scientific validation of C. sativa L. available in certain countries is required and demands to research its effect on cancer cell growth and progression. In the present study, several C. sativa L. samples were collected from various part of the world including Southern Africa and studied to determine their comparative cytotoxic and anti-angiogenic activity with exploring the possible mechanism of their action. Sixteen samples of C. sativa L. collected from various parts of the world and four extracts from each sample generated by 24-h successive maceration using hexane, dichloromethane (DCM), DCM: methanol (1:1) and methanol. Total flavonoid content (TFC) in each extract was quantified. Angiogenesis in Chick Chorioallantoic Membrane (CAM) was induced by vascular endothelial growth factor (VEGF) and l-arginine at the day 8th and the effect confirmed at the day 11th. Nitric oxide (NO) and matrix mettaloproteinase-1 (MMP-1) inhibition assays were performed to explore the possible mechanism of action. Cytotoxicity and VEGF inhibition assays were also performed in MCF-7 breast cancer cell line. The C. sativa L. of “Pondo” region, of the Eastern Cape, South Africa showed maximum inhibition of angiogenic index and inhibited the MMP-1 enzyme (whereas IC50 found < 20 μg/ml) as compared to other samples. The flavonoid enriched extracts inhibited the NO whereas IC50 ranged from 80.83-90.15 μg/ml. The C. sativa L. sample of Eastern Cape South Africa and Denmark (Danish) were found more cytotoxic (IC50 ~ 25 μg/ml at 48 h) and able to reduce extracellular VEGF level significantly in MCF-7 cells as *p < 0.05 found statistically. The result collectively indicated that C. sativa L. from “Pondo” region of Eastern Cape, South Africa showed maximum inhibitory effect on MCF-7 cell growth and angiogenesis due to ability to inhibit NO, MMP-1 and VEGF meriting further studies.