Rapid Downregulation of Cyclin D1 Induced by Geranylgeranoic Acid in Human Hepatoma Cells

Autor:	Takashi Muraguchi, Maiko Mitake, Yoshihiro Shidoji, Shohei Shimonishi, Chiharu Sakane, Kyoko Okamoto
Rok vydání:	2012
Předmět:	Proteasome Endopeptidase Complex Cancer Research Leupeptins Cyclin D Down-Regulation Medicine (miscellaneous) Retinoblastoma Protein Cyclin D1 Downregulation and upregulation Cell Line Tumor Humans Phosphorylation Cyclin Nutrition and Dietetics biology Reverse Transcriptase Polymerase Chain Reaction Kinase Cell Cycle Liver Neoplasms Retinoblastoma protein Hep G2 Cells Cell cycle Molecular biology Gene Expression Regulation Neoplastic Oncology Proteasome biology.protein Diterpenes E2F1 Transcription Factor
Zdroj:	Nutrition and Cancer. 64:473-480
ISSN:	1532-7914 0163-5581
DOI:	10.1080/01635581.2012.655401
Popis:	Geranylgeranoic acid (GGA) and its derivatives are currently under development as chemopreventive agents against second primary hepatoma in Japan. We aimed to evaluate chemoprevention targets of GGA and a surrogate marker of chemopreventive response to clarify the molecular mechanism of hepatoma chemoprevention with GGA. Human hepatoma-derived cell lines such as HuH-7, PLC/PRF/5, and HepG-2, were treated with GGA and its derivatives. Cellular dynamics of several cell-cycle-related proteins were assessed by either immunoblotting or immunofluorescence method. The cellular expression of cyclin D1 protein was suppressed immediately after GGA treatment. This reduction was partially blocked by pretreatment with 26S proteasome inhibitor MG-132, indicating that proteasomal degradation was involved in GGA-induced disappearance of cyclin D1. A phosphorylation of retinoblastoma protein (RB) at serine 780, a target site of cyclin D1-dependent kinase 4, was rapidly decreased in GGA-treated HuH-7 cells. Furthermore, subcellular fractionation, Western blotting, and immunofluorescence revealed GGA-induced nuclear accumulation of RB. These results strongly suggest that cyclin D1 may be a target of chemopreventive GGA in human hepatoma cells. GGA-induced rapid repression of cyclin D1, and a consequent dephosphorylation and nuclear translocation of RB, may influence cell cycle progression and may be relevant to GGA-induced cell death mechanisms.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dab000a44247f38f19d73fa2b2fe0e7f https://doi.org/10.1080/01635581.2012.655401 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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