Figure 3.

Mechanisms of action of the combined therapy of natural compounds and chemotherapeutic agents. Combination therapy presents an alternative to the therapeutic difficulties of cancer. (1) Inhibition of efflux pumps, induces the intracellular accumulation the chemotherapeutic agent; (2) Tumor cells increase the expression of genes related to the detoxification of xenobiotics; combined therapy provides inhibition of these mechanisms accompanied by an increase in the production of ROS. (3) Non-apoptotic cell death such as autophagy and necrosis are activated by combination therapy. (4) Proinflammatory cytokines act mainly due to the activation of the transcription factor NF-κB. This transcription factor can induce the expression of various genes that modulate apoptosis and promote cellular transformation, progression and chemoresistance; natural compounds with immunomodulatory activity have been reported as possible adjuvants to chemotherapy. (5) Resistance to chemotherapeutics can be generated by increased ability of cancer cells to repair DNA damage, thereby considerably reducing the efficacy of the drug. Inhibit the activity of the repair mechanisms and enhanced DNA damage increased cell death and reduced proliferation. These mechanisms result in decreased cell proliferation and metastatic capacity, reduced angiogenesis and in some cases increased apoptosis. Created with BioRender.com ABC: ATP binding cassette, ROS: reactive oxygen species.