Molecular mechanisms of bufadienolides and their novel strategies for cancer treatment.

Abstract

Bufadienolides are cardioactive C24 steroids with an α-pyrone ring at position C17. In the last ten years, accumulating studies have revealed the anticancer activities of bufadienolides and their underlying mechanisms, such as induction of autophagy and apoptosis, cell cycle disruption, inhibition of angiogenesis, epithelial-mesenchymal transition (EMT) and stemness, and multidrug resistance reversal. As Na+/K+-ATPase inhibitors, bufadienolides have inevitable cardiotoxicity. Short half-lives, poor stability, low plasma concentration and oral bioavailability in vivo are obstacles for their applications as drugs. To improve the drug potency of bufadienolides and reduce their side effects, prodrug strategies and drug delivery systems such as liposomes and nanoparticles have been applied. Therefore, systematic and recapitulated information about the antitumor activity of bufadienolides, with special emphasis on the molecular or cellular mechanisms, prodrug strategies and drug delivery systems, is of high interest. Here, we systematically review the anticancer effects of bufadienolides and the molecular or cellular mechanisms of action. Research advancements regarding bufadienolide prodrugs and their tumor-targeting delivery strategies are critically summarized. This work highlights recent scientific advances regarding bufadienolides as effective anticancer agents from 2011 to 2019, which will help researchers to understand the molecular pathways involving bufadienolides, resulting in a selective and safe new lead compound or therapeutic strategy with improved therapeutic applications of bufadienolides for cancer therapy.

• Authors: Li-Juan Deng, Yong Li, Ming Qi, Jun-Shan Liu, Sheng Wang, Li-Jun Hu, Yu-He Lei, Ren-Wang Jiang, Wei-Min Chen, Qi Qi, Hai-Yan Tian, Wei-Li Han, Bao-Jian Wu, Jia-Xu Chen, Wen-Cai Ye, Dong-Mei Zhang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 887 Pg. 173379 (Nov 15 2020) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 32758567 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• Bufanolides
• Prodrugs

Topics

• Angiogenesis Inhibitors (chemistry, metabolism, therapeutic use)
• Animals
• Antineoplastic Agents (chemistry, metabolism, therapeutic use)
• Apoptosis (drug effects, physiology)
• Bufanolides (chemistry, metabolism, therapeutic use)
• Cell Line, Tumor
• Humans
• Neoplasms (drug therapy, metabolism)
• Prodrugs (chemistry, metabolism, therapeutic use)