The Effects of Wild Yam Root ( Dioscorea Villosa) Extract in Human Triple Negative MDA-MB-231 Breast Cancer Cells

Abstract

Breast cancer (BC) is one of the leading causes of death among women worldwide. Triple negative breast cancer (TNBC) is one of the most aggressive subtypes of BC correlating with poor prognosis constituting 10-15% of all breast cancer cases. Wild yam root extract (WYE), Dioscorea villosa is a natural plant with anti-cancer properties known to contain glycoside saponins, steroidal saponins, diosgenin, alkaloids, starch, Phyto-sterols and tannins. Numerous in vitro high throughput (HTP) botanical chemotherapeutic cytotoxic screenings have shown promise for WYE as being toxic to a diverse range of abnormal cell types including, melanoma, glioma, neuroblastoma, and colon and breast cancers. Unique among the chemotherapeutic herbs , WYE contains a high content of detergent-like saponins, which cause cell lysis on direct contact through disruption of the phospholipid cell membrane interactions largely account for cell toxicity. In this study, the destructive effects of WYE on triple negative breast cancers (MDA-MB-231) were examined at sub-lethal concentrations where saponins do not contribute to lytic cell death. Cells were continuously monitored for overall viability and proliferation with confirmation studies performed using protein antibody arrays and ELISA. The findings reveal a concurrent loss of cell membrane potential and complete destruction of 2D and 3D cultures, corresponding to the rise in saponin content from the wild yam extract at high concentrations. At low concentrations, WYE shows a pro-inflammatory profile up- regulating Tumor Necrosis Factor (TNF) signaling and steroid biosynthesis related genes and induced cytostatic effects which block cell division, corresponding to loss of cell cycle transcripts. In conclusion, the toxic effects of WYE are likely to occur by lysis at higher concentrations, but at lower concentrations it evokes a pro-inflammatory cytostatic effect on BC cells.