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Effects of tyroserleutide on gene expression of calmodulin and PI3K in hepatocellular carcinoma
Author(s) -
Zhao Lan,
Zhao Qian,
Lu Rong,
Fu Zheng,
Zhu Zhifeng,
Jia Jing,
Wang Song,
Shi Linxi,
Jian Xu,
Yao Zhi
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.21409
Subject(s) - pi3k/akt/mtor pathway , calmodulin , messenger rna , p110α , protein subunit , biology , signal transduction , hepatocellular carcinoma , cancer research , microbiology and biotechnology , chemistry , gene , biochemistry , enzyme
Tyroserleutide (YSL) is a tripeptide compound that has exhibited inhibitory effects on hepatocellular carcinoma in our previous research. The mechanism of this antitumor activity involves the second messenger, Ca 2+ . Ca 2+ influences cell function through the Ca 2+ /calmodulin (CaM) pathway, and abnormality of the Ca 2+ /CaM system correlates closely with the occurrence of tumors. In addition, CaM associates with phosphatidylinositol 3 kinase (PI3K), thereby enhancing the activity of PI3K, which promotes cell proliferation. In order to investigate its anti‐tumor mechanism, we studied the effects of YSL on CaM protein expression and mRNA level, PI3K activity, PI3K regulatory subunit p85 protein expression and mRNA level, and the mRNA level of PI3K catalytic subunits p110α and p110γ in human hepatocellular carcinoma BEL‐7402 xenograft tumors in nude mice. Our results showed that YSL decreased the mRNA level and protein expression of CaM, inhibited the activity of PI3K, and reduced the mRNA level and protein expression of the PI3K regulatory subunit p85 and mRNA level of PI3K catalytic subunits p110α and p110γ. Accordingly, it is suggestive that the anti‐tumor effects of YSL may be mediated by down regulation of CaM and PI3K subunits p85 and p110, influencing the signal transduction pathway in the tumor cells and perhaps overcoming the dysfunctional PI3K activity in tumors. J. Cell. Biochem. 103: 471–478, 2008. © 2007 Wiley‐Liss, Inc.