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Resveratrol induces cell death in cervical cancer cells through apoptosis and autophagy

García-Zepeda, Sihomara P.a; García-Villa, Enriquea; Díaz-Chávez, Joséb; Hernández-Pando, Rogelioc; Gariglio, Patricioa

European Journal of Cancer Prevention: November 2013 - Volume 22 - Issue 6 - p 577–584
doi: 10.1097/CEJ.0b013e328360345f
Research Paper: Gynaecological Cancer

Cervical neoplasia is one of the most frequent cancers in women and is associated with high-risk human papillomavirus (HPV) infection. Resveratrol, a natural polyphenolic phytochemical, has received considerable interest on the basis of its potential as a chemopreventive agent against human cancer. In this work, we analyzed the type of cell death induced by resveratrol in several cervical cancer cell lines. Resveratrol treatment (150–250 µmol/l) for 48 h increased cell cycle arrest at the G1 phase in C33A (with mutation in p53) and HeLa cells (HPV18 positive), as well as in CaSki and SiHa cell lines (HPV16 positive). Resveratrol treatment induced apoptosis in all cell lines, particularly in CaSki cells, as measured by Annexin-V flow cytometry analysis. There was a decrease in the mitochondrial membrane potential (apoptosis) in HeLa, CaSki, and SiHa cells and an increased lysosomal permeability (autophagy) in C33A, CaLo (HPV18 positive), and HeLa cell lines. Furthermore, when we used the IC50 of each line, we found that resveratrol produces a similar effect, suggesting that this effect is not dependent on the concentration of resveratrol. Interestingly, after resveratrol treatment, the expression of p53 was decreased in HPV18-positive cell lines (CaLo and HeLa) and increased in HPV16-positive cell lines (CaSki and SiHa) and C33A cells. The expression of p65 (an NF-κB subunit) was decreased after treatment in all cell lines except SiHa cells. These data indicate that resveratrol uses different mechanisms to induce cell death in cell lines derived from cervical cancer.

aDepartment of Genetics and Molecular Biology, Center for Research and Advance Studies, National Polytechnic Institute

bUnit of Biomedical Research in Cancer, Institute of Biomedical Research, UNAM/National Cancer Institute

cDepartment of Experimental Pathology, National Institute for Medical Sciences and Nutrition Salvador Zubiran, Mexico City, Mexico

All supplementary digital content is available directly from the corresponding author.

Correspondence to Patricio Gariglio, PhD, Department of Genetics and Molecular Biology, Center for Research and Advance Studies, National Polytechnic Institute, IPN Av. 2508, PO Box 07360, Mexico City, Mexico Tel: +52 555 747 3337; fax: +52 555 747 3931; e-mail: vidal@cinvestav.mx

Received August 15, 2012

Accepted February 11, 2013

© 2013 Lippincott Williams & Wilkins, Inc.