Berberine—A potent chemosensitizer and chemoprotector to conventional cancer therapies

Chemotherapy and radiotherapy are mainstay treatments for cancer patients. However, their clinical outcomes are highly limited by the resistance of malignant tumors to these therapies and the incurrence of serious damages in vital organs. This in turn necessitates the development of adjunct drugs that overcomes chemo/radioresistance in refractory cancers and protects vital organs from the cytotoxic effects of cancer therapies. In recent years, Berberine (BBR), a natural isoquinoline alkaloid has garnered more attention due to its potent chemosensitizing and chemoprotective properties. BBR effectively sensitizes refractory cancers to chemotherapy and radiotherapy by ameliorating the diverse events underlying therapy resistance. Furthermore, it protects the heart, liver, lungs, and kidneys from severe damages caused by these therapies. In this review, we discuss the molecular mechanisms underlying the chemo/radiosensitizing and chemo/radioprotective potential of BBR during cancer treatment. Also, we highlight the limitations that hamper the clinical application of BBR as an adjunct drug and how novel innovations have been made in recent years to circumvent these challenges.