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Proteomic analysis of differentially expressed proteins in human hepatocellular carcinoma cells after 4‐O‐carboxymethyl ascochlorin treatment
Author(s) -
Kang Jeong Han,
Maurizi Michael R.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb97
Subject(s) - protein disulfide isomerase , blot , immunostaining , hepatocellular carcinoma , chemistry , microbiology and biotechnology , autophagy , proteomics , biochemistry , apoptosis , cancer research , biology , enzyme , immunohistochemistry , immunology , gene
The synthetic derivative of ascochlorin, 4‐O‐carboxymethyl ascochlorin (AS‐6), ameliorates type II diabetes in mice and also activates PPAR‐γ. We performed a proteomic analysis of human hepatocellular carcinoma HepG2 cells exposed to AS‐6 to identify proteins that accumulated to in higher or lower amounts. We found 58 differentially expressed proteins representing 55 unique protein species. AS‐6 treatment led to up‐regulation of ER stress‐related proteins including glucose‐regulated protein 78 (BiP/GRP78) and protein disulfide isomerase (PDI). The observed changes in expression of GRP78, PDI, and a select group of other proteins were validated by real‐time PCR, Western blotting, and immunostaining. We propose that AS‐6 exerts its cytotoxic effect via a mechanism initiated by ER stress followed by autophagy. Because it activates autophagic pathways, AS‐6 has potential as a drug lead for anticancer agents with therapeutic utility.