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Upregulation of heat shock protein 27 confers resistance to actinomycin D ‐induced apoptosis in cancer cells
Author(s) -
Ma Wenbo,
Teng Yan,
Hua Hui,
Hou Jinlin,
Luo Ting,
Jiang Yangfu
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12432
Subject(s) - hsp27 , downregulation and upregulation , heat shock protein , gene knockdown , cancer cell , apoptosis , cancer research , hsf1 , hsp90 inhibitor , biology , microbiology and biotechnology , hsp90 , chemistry , hsp70 , cancer , biochemistry , genetics , gene
Actinomycin D (Act D ) is a general transcriptional inhibitor that is approved for the treatment of sarcomas, and W ilms, 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 ( HSP s) and the expression and roles of HSP 27 in Act D ‐induced cancer cell apoptosis. We show that Act D upregulates HSP 27 and HSP 70 expression in cancer cells, whereas it inhibits HSP 90 expression. The upregulation of HSP 27 by Act D is not attributable to changes in HSP27 transcription or HSP 27 synthesis. HSP 27 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 HSP 27 represents an adaptive response that compromises the anticancer activity of Act D .