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Evidence-Based Complementary and Alternative Medicine
Volume 2012 (2012), Article ID 980658, 11 pages
http://dx.doi.org/10.1155/2012/980658
Research Article

Alternative Pathways of Cancer Cell Death by Rottlerin: Apoptosis versus Autophagy

1Department of Physiology, University of Siena, Via Aldo Moro, 7-53100 Siena, Italy
2Department of Biology and Evolution, University of Ferrara, Via Luigi Borsari 46, 44100 Ferrara, Italy
3Department of Food and Nutrition, Kyung Hee University, Seoul 130-701, Republic of Korea
4Department of Cytokinetics, Institute of Biophysics AS CR, v.v.i. Kralovopolska 135, 612 65 Brno, Czech Republic
5Center of Biomolecular and Cellular Engineering and International Clinical Research Center, St. Anne’s University Hospital Brno, 1656 91 Brno, Czech Republic
6Department of Biomedical Sciences, University of Siena, Via Aldo Moro, 7-53100 Siena, Italy

Received 22 October 2012; Revised 26 November 2012; Accepted 28 November 2012

Academic Editor: Chun-Tao Che

Copyright © 2012 Claudia Torricelli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Since the ability of cancer cells to evade apoptosis often limits the efficacy of radiotherapy and chemotherapy, autophagy is emerging as an alternative target to promote cell death. Therefore, we wondered whether Rottlerin, a natural polyphenolic compound with antiproliferative effects in several cell types, can induce cell death in MCF-7 breast cancer cells. The MCF-7 cell line is a good model of chemo/radio resistance, being both apoptosis and autophagy resistant, due to deletion of caspase 3 gene, high expression of the antiapoptotic protein Bcl-2, and low expression of the autophagic Beclin-1 protein. The contribution of autophagy and apoptosis to the cytotoxic effects of Rottlerin was examined by light, fluorescence, and electron microscopic examination and by western blotting analysis of apoptotic and autophagic markers. By comparing caspases-3-deficient ( ) and caspases-3-transfected MCF-7 cells ( ), we found that Rottlerin induced a noncanonical, Bcl-2-, Beclin 1-, Akt-, and ERK-independent autophagic death in the former- and the caspases-mediated apoptosis in the latter, in not starved conditions and in the absence of any other treatment. These findings suggest that Rottlerin could be cytotoxic for different cancer cell types, both apoptosis competent and apoptosis resistant.