Despite the significant advances and mechanistic understanding of tumor processes, therapeutic agents against different types of cancer still have a high rate of recurrence associated with the development of resistance by tumor cells. This chemoresistance involves several mechanisms, including the programming of glucose metabolism, mitochondrial damage, and lysosome dysfunction. However, combining several anticancer agents can decrease resistance and increase therapeutic efficacy. Furthermore, this treatment can improve the effectiveness of chemotherapy. This work focuses on the recent advances in using natural bioactive molecules derived from phenolic compounds isolated from medicinal plants to sensitize cancer cells towards chemotherapeutic agents and their application in combination with conventional anticancer drugs. Dietary phenolic compounds such as resveratrol, gallic acid, caffeic acid, rosmarinic acid, sinapic acid, and curcumin exhibit remarkable anticancer activities through sub-cellular, cellular, and molecular mechanisms. These compounds have recently revealed their capacity to increase the sensitivity of different human cancers to the used chemotherapeutic drugs. Moreover, they can increase the effectiveness and improve the therapeutic index of some used chemotherapeutic agents. The involved mechanisms are complex and stochastic, and involve different signaling pathways in cancer checkpoints, including reactive oxygen species signaling pathways in mitochondria, autophagy-related pathways, proteasome oncogene degradation, and epigenetic perturbations.
Keywords: cancer; chemotherapy; combination treatment; dietary phenolic compounds; drugs resistance; drugs sensibilization.