Hsp70 promotes chemoresistance by blocking Bax mitochondrial translocation in ovarian cancer cells

Cisplatin can induce apoptosis in ovarian cancer cells through the mitochondrial death pathway, and dysregulation of this pathway contributes to cisplatin resistance in ovarian cancer cells. Here we show that cisplatin induces mitochondrial proteins such as Smac/DIABLO, Cytochrome c, and HrtA2/Omi r...

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Bibliographic Details
Published in:Cancer letters 2012-08, Vol.321 (2), p.137-143
Main Authors: Yang, Xiaokui, Wang, Jiandong, Zhou, Ying, Wang, Yamei, Wang, Shuyu, Zhang, Weiyuan
Format: Article
Language:English
Subjects:
animal ovaries
Apoptosis
Apoptosis - drug effects
Bax
bcl-2-Associated X Protein - metabolism
Biotechnology
Blotting, Western
Cancer therapies
Caspases - metabolism
Cell Culture Techniques
Cell Line, Tumor
cisplatin
Cisplatin - pharmacology
Cisplatin-resistance
Cytochrome
cytochrome c
cytosol
death
Drug Resistance, Neoplasm - drug effects
Female
Fractions
Hematology, Oncology and Palliative Medicine
Hsp70
HSP70 Heat-Shock Proteins - metabolism
Humans
Intracellular Signaling Peptides and Proteins - metabolism
Laboratories
Mitochondria
Mitochondria - metabolism
Mitochondria - physiology
Mitochondrial Proteins - metabolism
Ovarian cancer
ovarian neoplasms
Ovarian Neoplasms - metabolism
Protein Transport
Proteins
Proto-Oncogene Proteins c-bcl-2 - metabolism
Science
Sucrose
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Summary:Cisplatin can induce apoptosis in ovarian cancer cells through the mitochondrial death pathway, and dysregulation of this pathway contributes to cisplatin resistance in ovarian cancer cells. Here we show that cisplatin induces mitochondrial proteins such as Smac/DIABLO, Cytochrome c, and HrtA2/Omi release to the cytosol and apoptosis in cisplatin-sensitive, but not -resistant ovarian cancer cells. Bax translocation to mitochondria is required for mitochondrial protein release and cisplatin-induced apoptosis in human ovarian cancer cells. Hsp70 is highly expressed in cisplatin-resistant cells. Hsp70 promotes chemoresistance, in part, by blocking Bax translocation to the mitochondria and mitochondrial protein release to cytosol in human ovarian cancer cells.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2012.01.030