Upregulation of heat shock protein 27 confers resistance to actinomycin D-induced apoptosis in cancer cells.

Abstract	Actinomycin D (Act D) is a general transcriptional inhibitor that is approved for the treatment of sarcomas, and Wilms, germ cell and trophoblastic tumors. Little is known about the molecular mechanisms that dictate the sensitivity of cancer cells to Act D. In this study, we investigated the effects of Act D on heat shock proteins (HSPs) and the expression and roles of HSP27 in Act D-induced cancer cell apoptosis. We show that Act D upregulates HSP27 and HSP70 expression in cancer cells, whereas it inhibits HSP90 expression. The upregulation of HSP27 by Act D is not attributable to changes in HSP27 transcription or HSP27 synthesis. HSP27 knockdown leads to an increase in Act D-induced caspase 3 and caspase 7 cleavage, and sensitizes rhabdosarcoma cells and breast cancer cells to Act D-induced apoptosis. We conclude that upregulation of HSP27 represents an adaptive response that compromises the anticancer activity of Act D.
Authors	Wenbo Ma, Yan Teng, Hui Hua, Jinlin Hou, Ting Luo, Yangfu Jiang
Journal	The FEBS journal (FEBS J) Vol. 280 Issue 18 Pg. 4612-24 (Sep 2013) ISSN: 1742-4658 [Electronic] England
PMID	23848600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	© 2013 FEBS.
Chemical References	Antibiotics, Antineoplastic HSP27 Heat-Shock Proteins HSP70 Heat-Shock Proteins HSP90 Heat-Shock Proteins HSPB1 protein, human Heat-Shock Proteins Molecular Chaperones RNA, Small Interfering Dactinomycin Caspase 3 Caspase 7
Topics	Adaptation, Physiological Antibiotics, Antineoplastic (pharmacology) Apoptosis (drug effects) Caspase 3 (genetics, metabolism) Caspase 7 (genetics, metabolism) Cell Line, Tumor Dactinomycin (pharmacology) Drug Resistance, Neoplasm Gene Expression Regulation, Neoplastic (drug effects) HSP27 Heat-Shock Proteins (agonists, genetics, metabolism) HSP70 Heat-Shock Proteins (agonists, genetics, metabolism) HSP90 Heat-Shock Proteins (antagonists & inhibitors, genetics, metabolism) Heat-Shock Proteins Humans Molecular Chaperones Proteolysis RNA, Small Interfering (genetics) Signal Transduction

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