Regulatory Effects of Resveratrol on Antioxidant Enzymes: a Mechanism of Growth Inhibition and Apoptosis Induction in Cancer Cells

Abstract

Resveratrol (RSV) is a natural polyphenol that is known as a powerful chemopreventive and chemotherapeutic anticancer molecule. This study focused on the effects of RSV on the activities and expression levels of antioxidant enzymes in the cancer cells. Prostate cancer PC-3 cells, hepatic cancer HepG2 cells, breast cancer MCF-7 cells and the non-cancerous HEK293T kidney epithelial cells were treated with a wide range of RSV concentrations (10-100 μM) for 24-72 h. Cell growth was estimated by trypan blue staining, activities of the antioxidant enzymes were measured spectrophotometrically, expression levels of the antioxidant enzymes were quantified by digitalizing the protein band intensities on Western blots, and the percentage of apoptotic cells was determined by flow cytometry. Treatment with a low concentration of RSV (25 μM) significantly increased superoxide dismutase (SOD) activity in PC-3, HepG2 and MCF-7 cells, but not in HEK293T cells. Catalase (CAT) activity was increased in HepG2 cells, but no effect was found on glutathione peroxidase (GPX) upon RSV treatment. RSV-induced SOD2 expression was observed in cancer cells, although the expression of SOD1, CAT and GPX1 was unaffected. Apoptosis increased upon RSV treatment of cancer cells, especially in PC-3 and HepG2 cells. Together, our data demonstrated that RSV inhibits cancer cell growth with minimal effects on non-cancerous cells. We postulate that the disproportional up-regulation of SOD, CAT and GPX expression and enzymatic activity in cancer cells results in the mitochondrial accumulation of H2O2, which in turn induces cancer cell apoptosis.

Antioxidant Effect of Berberine and its Phenolic Derivatives Against Human Fibrosarcoma Cells

“…The relationship between SOD-CAT function and mechanistic pathway can be used to suggest that the increasing of SOD expression should elevate the H 2 O 2 concentration from •O 2 - (Khan et al, 2013). In addition, the decreasing of CAT expression made the redox imbalance because of the less decomposition of H 2 O 2 (Khan et al, 2010).…”

“…In contrast, up-regulation or enhancement of antioxidant enzyme activities including SOD, CAT, and GPx has been proposed as an effective strategy for both cancer prevention and therapy (Khan et al, 2013). For example, progestin induction for catalase activity has been proven to be effective against breast cancer (Petit et al, 2009).…”

Effect of Vitamins on the Quality of Insemination Doses of Bulls

“…Studies has also demonstrated that antioxidants protect spermatozoa from ROS produced by leukocytes, prevent DNA fragmentation, improve semen quality, reduce cryodamage to spermatozoa, block premature sperm maturation, provide an overall stimulation to the sperm cells and improve assisted reproductive techniques outcome (Agarwal et al, 2007; Tvrda et al, 2013). On the other hand, studies have also shown that the decreased activities of antioxidant enzymes are associated with various types of cancer such as prostate cancer, bladder cancer, breast cancer, hepatic cancer, multiple myeloma (Khan et al 2013). The synthetic antioxidants are one of the solutions; however, the naturally occurring substances are preferable due its chemical diversity, structural complexity, availability, intrinsic biologic activity or lack of substantial toxic effects (Tvrdá et al, 2015a).…”

Preventive Effects of Resveratrol against Azoxymethane Induced Damage in Rat Liver

“…It has a potent antioxidant (Khan et al, 2013) and antiinflammatory (Pallarès et al, 2012) properties, which can play a crucial role against carcinogenesis (Bishayee et al, 2010). Many experimental studies are conduced to support a key role of reactive oxygen species (ROS) in the numerous mechanisms of seemingly unrelated hepatopathies (Zigdon et al, 2013).…”