Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms

作者：Zhichao Xing, Anping Su, Mi Li, Yujie Zhang, Ting He, Yuxuan Qiu, Tao Wei, Zhihui Li, Jingqiang Zhu, Wenshuang Wu · 发表于：Drug Design Development and Therapy · 年份：2023 · DOI：10.2147/dddt.s422512 · 被引用次数：51 · 研究领域：Phytochemicals and Medicinal Plants

Abstract: Cancer, as the leading cause of death worldwide, poses a serious threat to human health, making the development of effective tumor treatments a significant challenge. Natural products continue to serve as crucial resources for drug discovery. Among them, Withaferin A (WA), the most active phytocompound extracted from the renowned dietary supplement Withania somnifera (L.) Dunal, exhibits remarkable anti-tumor efficacy. In this manuscript, we aim to comprehensively summarize the pharmacological characteristics of WA as a potential anti-tumor drug candidate, with the objective of contributing to its further development and the discovery of prospective drugs. Through an extensive review of literature from PubMed, Science Direct, and Web of Science, we have gathered substantial evidence showcasing WA’s significant anti-tumor effects against a wide range of cancers in both in vitro and in vivo studies. Mechanistically, WA exerts its anti-tumor influence by inducing cell cycle arrest, apoptosis, autophagy, and ferroptosis. Additionally, it inhibits cell proliferation, cancer stem cells, tumor metastasis, and also suppresses epithelial-mesenchymal transition (EMT) and angiogenesis. Several studies have identified direct target proteins of WA, such as vimentin, Hsp90, annexin II and mFAM72A, while BCR-ABL, Mortalin (mtHsp70), Nrf2, and c-MYB are potential targets of WA. Notwithstanding its remarkable anti-tumor efficacy, there are some limitations associated with WA, includ...