Cytokines, the Tumor Microenvironment, and Selected Plant-Derived Natural Products

Cytokines are produced by immune and other cells and work as cellular messengers to regulate an immune response and other biological processes. As the main components of the tumor microenvironment (TME), cytokines are involved in the major events of cancer development, including cancer and cancer stem cell proliferation, angiogenesis, invasion, and metastasis. They also modulate immune functions and inhibit tumor progression and resistance to conventional therapies and thus have been regarded as promising targets for cancer treatment. Recently, tumor reversibility has attracted wide interest, for which the TME plays a critical role. Many plant-derived products exhibit potential tumor-inhibitory and cytokine-modulatory activities, including andrographolide, artemisinin, berberine, camptothecin, capsaicin, curcumin, digoxin, morphine, paclitaxel, and vinblastine, indicating their possible use in cancer reversal. Thus, in the present review, correlations among cytokines, the TME, tumor immunity, and tumor reversibility have been discussed, and the potential effects of selected plant-derived natural products on these issues have been addressed.