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Protein phosphatase 1 activation and alternative splicing of Bcl‐X and Mcl‐1 by EGCG + ibuprofen
Author(s) -
Kim Myoung H.
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21725
Subject(s) - lncap , apoptosis , ibuprofen , chemistry , downregulation and upregulation , cell growth , rna splicing , alternative splicing , phosphatase , cell culture , microbiology and biotechnology , biology , cancer cell , cancer research , messenger rna , phosphorylation , biochemistry , pharmacology , gene , cancer , rna , genetics
Epigallocatechin‐3‐gallate (EGCG) and ibuprofen synergistically act to suppress proliferation and enhance apoptosis of prostate cancer cell lines, PC‐3 and LNCaP. The purpose of this study was to investigate the mechanism of underlying this synergism. Most interestingly, EGCG + ibuprofen treatment in PC‐3 cells resulted in altering the ratio of the splice variants of Bcl‐X and Mcl‐1, downregulating the mRNA levels of anti‐apoptotic Bcl‐X(L) and Mcl‐1(L) with a concomitant increase in the mRNA levels of pro‐apoptotic Bcl‐X(s) and Mcl‐1(s). However, there were no apparent changes in splicing variants in either ibuprofen or EGCG treated cells. Induction of alternative splicing was correlated with increased activity of protein phosphatase 1 (PP1) in EGCG + ibuprofen‐treated cells, since pretreatment with calyculin A and tautomycin blocked EGCG + ibuprofen‐induced alternative splicing in PC‐3 cells in contrast to pretreatment with okadaic acid. On the other hand, EGCG + ibuprofen treatment in LNCaP cells did not alter splicing variants of Bcl‐X and Mcl‐1, despite the increase in protein phosphatase activity. In both cell lines, EGCG + ibuprofen inhibited cell proliferation synergistically. Taken together, this study demonstrate for the first time that EGCG + ibuprofen upregulated PP1 activity, which in turn induced alternative splicing of Bcl‐X and Mcl‐1 in a cell‐type specific manner. Our study also demonstrates that the activation of PP1 contributes to the alternative splicing of Mcl‐1. J. Cell. Biochem. 104: 1491–1499, 2008. © 2008 Wiley‐Liss, Inc.