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Mol. Cells 2013; 35(3): 219-225

Published online February 26, 2013

https://doi.org/10.1007/s10059-013-2259-z

© The Korean Society for Molecular and Cellular Biology

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

Md. Asaduzzaman Khan, Han-chun Chen, Xin-xing Wan, Mousumi Tania, Ai-hua Xu, Fang-zhi Chen, and Dian-zheng Zhang

Department of Biochemistry, School of Biological Science and Technology, Central South University, Changsha, Hunan 410013, China, Department of Urology, the Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China, Department of Biochemistry/Molecular Biology, Philadelphia College of Osteopathic Medicine, Philadelphia, PA19131, USA

Received: October 8, 2013; Revised: January 8, 2013; Accepted: January 10, 2013

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.

Keywords Apoptosis, HepG2 cells, MCF-7 cells, PC-3 cells, resveratrol, superoxide dismutase

Article

Research Article

Mol. Cells 2013; 35(3): 219-225

Published online March 31, 2013 https://doi.org/10.1007/s10059-013-2259-z

Copyright © The Korean Society for Molecular and Cellular Biology.

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

Md. Asaduzzaman Khan, Han-chun Chen, Xin-xing Wan, Mousumi Tania, Ai-hua Xu, Fang-zhi Chen, and Dian-zheng Zhang

Department of Biochemistry, School of Biological Science and Technology, Central South University, Changsha, Hunan 410013, China, Department of Urology, the Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China, Department of Biochemistry/Molecular Biology, Philadelphia College of Osteopathic Medicine, Philadelphia, PA19131, USA

Received: October 8, 2013; Revised: January 8, 2013; Accepted: January 10, 2013

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.

Keywords: Apoptosis, HepG2 cells, MCF-7 cells, PC-3 cells, resveratrol, superoxide dismutase

Mol. Cells
Sep 30, 2023 Vol.46 No.9, pp. 527~572
COVER PICTURE
Chronic obstructive pulmonary disease (COPD) is marked by airspace enlargement (emphysema) and small airway fibrosis, leading to airflow obstruction and eventual respiratory failure. Shown is a microphotograph of hematoxylin and eosin (H&E)-stained histological sections of the enlarged alveoli as an indicator of emphysema. Piao et al. (pp. 558-572) demonstrate that recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) significantly reduces the extended airspaces of the emphysematous alveoli by increasing the levels of TGF-β receptor I and SIRT1/6, as a previously unrecognized mechanism in human alveolar epithelial cells, and consequently mitigates COPD.

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