Title:Resveratrol as an Enhancer of Apoptosis in Cancer: A Mechanistic Review
Volume: 21
Issue: 17
Author(s): Milad Ashrafizadeh, Shahram Taeb, Hamed Haghi-Aminjan, Shima Afrashi, Kave Moloudi, Ahmed E. Musa, Masoud Najafi*Bagher Farhood*
Affiliation:
- Medical Technology Research Center, Kermanshah University of Medical Sciences, Kermanshah,Iran
- Department of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan,Iran
Keywords:
Resveratrol, cancer, apoptosis, NF-κB, COX-2, mitochondria, hypoxia.
Abstract: The resistance to therapy of cancer cells is a challenge for achieving an appropriate therapeutic
outcome. Cancer (stem) cells possess several mechanisms for increasing their survival following exposure to
toxic agents such as chemotherapy drugs, radiation, as well as immunotherapy. Evidences show that apoptosis
plays a key role in the response of cancer (stem) cells and their multi-drug resistance. Modulation of both
intrinsic and extrinsic pathways of apoptosis can increase the efficiency of tumor response and amplify the
therapeutic effects of radiotherapy, chemotherapy, targeted therapy, and also immunotherapy. To date, several
agents, as adjuvant, have been proposed to overcome the resistance of cancer cells to apoptosis. Natural products
are interesting because of the low toxicity on normal tissues. Resveratrol is a natural herbal agent that has shown
interesting anti-cancer properties. It has been shown to kill cancer cells selectively while protecting normal cells.
Resveratrol can augment reduction/oxidation (redox) reactions, thus increases the production of ceramide and the
expression of apoptosis receptors, such as Fas Ligand (FasL). Resveratrol also triggers some pathways which
induce the mitochondrial pathway of apoptosis. On the other hand, resveratrol has an inhibitory effect on antiapoptotic
mediators, such as Nuclear Factor κ B (NF-κB), Cyclooxygenase-2 (COX-2), Phosphatidylinositol 3–
Kinase (PI3K), and mTOR. In this review, we explain the modulatory effects of resveratrol on apoptosis, which
can augment the therapeutic efficiency of anti-cancer drugs or radiotherapy.
