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

Biomed Pharmacother. 2021 Feb:134:111124. doi: 10.1016/j.biopha.2020.111124. Epub 2021 Jan 9.

Abstract

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.

Keywords: Naturally occurring medicinal compounds; Triple-negative breast cancer; Withaferin-A.

Publication types

  • Review

MeSH terms

  • Anticarcinogenic Agents / adverse effects
  • Anticarcinogenic Agents / pharmacokinetics
  • Anticarcinogenic Agents / therapeutic use*
  • Cell Transformation, Neoplastic / drug effects*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Signal Transduction
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology
  • Triple Negative Breast Neoplasms / prevention & control*
  • Withanolides / adverse effects
  • Withanolides / pharmacokinetics
  • Withanolides / therapeutic use*

Substances

  • Anticarcinogenic Agents
  • Withanolides
  • withaferin A