Natural products for enhancing the sensitivity or decreasing the adverse effects of anticancer drugs through regulating the redox balance

Redox imbalance is reported to play a pivotal role in tumorigenesis, cancer development, and drug resistance. Severe oxidative damage is a general consequence of cancer cell responses to treatment and may cause cancer cell death or severe adverse effects. To maintain their longevity, cancer cells can rescue redox balance and enter a state of resistance to anticancer drugs. Therefore, targeting redox signalling pathways has emerged as an attractive and prospective strategy for enhancing the efficacy of anticancer drugs and decreasing their adverse effects. Over the past few decades, natural products (NPs) have become an invaluable source for developing new anticancer drugs due to their high efficacy and low toxicity. Increasing evidence has demonstrated that many NPs exhibit remarkable antitumour effects, whether used alone or as adjuvants, and are emerging as effective approaches to enhance sensitivity and decrease the adverse effects of conventional cancer therapies by regulating redox balance. Among them are several novel anticancer drugs based on NPs that have entered clinical trials. In this review, we summarize the synergistic anticancer effects and related redox mechanisms of the combination of NPs with conventional anticancer drugs. We believe that NPs targeting redox regulation will represent promising novel candidates and provide prospects for cancer treatment in the future. An abnormal redox microenvironment plays a critical role in the tumorigenesis, development, and drug resistance of cancer.NPs can selectively act as pro-oxidants, inducing cytotoxicity in cancer cells, while also serving as antioxidants and protectors in normal cells for detoxification.NPs play a dual role in increasing the sensitivity and reversing the drug resistance of cancer cells, primarily through pro-oxidant action and, in some cases, through antioxidant action.The heterogeneities in cellular and molecular biology provide the potential basis for the diverse regulation of NPs on the redox state.The advances in novel redox-sensitive materials and clinical applications of NPs offer promising prospects.