Eun-Ryeong Hahm, Su-Hyeong Kim, Shivendra V Singh
Prevention of breast cancer is feasible because many risk factors for this malignancy are known (e.g., family history, reproductive factors, etc.). Medicinal plants and/or their bioactive phytochemicals are attractive for the prevention of early onset of breast cancer due to their generally favorable safety profile. Root extract of Withania somnifera (Ashwagandha) is a key ingredient in Ayurvedic medicine practiced in India for thousands of years. Preclinical research has established that withaferin A (WA) is primarily responsible for the anticancer effect of Ashwagandha. At cellular level, WA treatment inhibits the growth of human breast cancer cells by causing G2/M phase cell cycle arrest and apoptosis induction and suppressing the self-renewal of breast cancer stem-like cells. On the other hand, normal mammary epithelial cells are resistant to apoptosis induction by WA, which is a desirable characteristic of cancer preventive interventions. More importantly, WA administration prevents luminal type, human epidermal growth factor receptor 2-driven, and basal-like breast cancer development in rodents without causing any side effects. This review article not only succinctly summarizes preclinical evidence for anticancer effects of WA but also conceptualizes on high-risk women and men who may benefit from Ashwagandha intervention for prevention of early onset of breast cancer or prevention of bone metastasis of breast cancer.