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Alternative Pathways of Cancer Cell Death by Rottlerin: Apoptosis versus Autophagy
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SYSNO ASEP 0440779 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Alternative Pathways of Cancer Cell Death by Rottlerin: Apoptosis versus Autophagy Author(s) Torricelli, C. (IT)
Salvadori, S. (IT)
Valacchi, G. (IT)
Souček, Karel (BFU-R) RID, ORCID
Slabáková, Eva (BFU-R) RID, ORCID, RID, RID
Muscettola, M. (IT)
Volpi, N. (IT)
Maioli, E. (IT)Number of authors 8 Source Title Evidence-based Complementary and Alternative Medicine - ISSN 1741-427X
Roč. 2012, NOV (2012), s. 1-11 /AN 980658/Number of pages 11 s. Publication form Online - E Language eng - English Country GB - United Kingdom Keywords PKC-DELTA ; KAPPA-B ; CARCINOMA CELLS Subject RIV BO - Biophysics R&D Projects GPP301/12/P407 GA ČR - Czech Science Foundation (CSF) Institutional support BFU-R - RVO:68081707 UT WOS 000312865700001 DOI https://doi.org/10.1155/2012/980658 Annotation 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 (MCF-7(3def)) and caspases-3-transfected MCF-7 cells (MCF-7(3trans)), 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. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2015
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