Implications of Withaferin-A for triple-negative breast cancer chemoprevention

• Published in: Biomedicine & pharmacotherapy 2021-02, Vol.134, p.111124, Article 111124
• Main Authors: Mallipeddi, Harshini, Thyagarajan, Anita, Sahu, Ravi P.
• Format: Article
• Language: English
• Subjects: Naturally occurring medicinal compounds; Triple-negative breast cancer; Withaferin-A
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.111124

The cellular mechanisms of WA in the chemoprevention of breast cancer. The sign ↑ denotes upregulation or increased expression, ↓ downregulation or decreased expression, and ⊥ inhibition or suppression. [Display omitted] Triple-negative breast cancer (TNBC) accounts for about 15 % of all breast cancer cases, and unlike other malignancies, it lacks definite prognostic markers. While improved survival responses have been documented with the ongoing therapeutic approaches, the development of tumor resistance mechanisms to these treatment options pose major challenges in the treatment of TNBC. Notably, naturally occurring medicinal compounds have been studied extensively for their anti-neoplastic activities in cancer models including breast cancer due to their safe and non-deleterious effects. Among various dietary compounds, Withaferin-A (WA), a phytochemical derived from an ayurvedic medicinal plant, Withania somnifera has been characterized to possess anti-inflammatory and anti-cancer properties. Importantly, multiple studies have shown that WA exhibits promising anti-tumoral activities against in-vitro and in-vivo experimental models of TNBC and that its combination has been documented to enhance chemotherapy efficacy. The current review highlights the mechanistic insights with recent updates including the pharmacokinetics parameters and implications of WA against breast cancer with major emphasis on TNBC.