Document Detail

Perifosine induces cell cycle arrest and apoptosis in human hepatocellular carcinoma cell lines by blockade of Akt phosphorylation.
MedLine Citation:
PMID:  20842425     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Hepatocellular carcinoma (HCC) is one of the most common solid cancers, representing the third cause of cancer-related death among cirrhotic patients. Treatment of advanced HCC has become a very active area of research. Perifosine, a new synthetic alkylphospholipid Akt inhibitor, has shown anti-tumor activity by inhibition of Akt phosphorylation. In this study, the effect of perifosine on the cell proliferation and apoptosis in hepatoma cells has been investigated. Cell growth inhibition was detected by MTT assay, cell cycle was analyzed by flow cytometry, AnnexinV-FITC apoptosis detection kit was used to detect cell apoptosis, and protein expression was examined by Western blotting analysis. Our present studies showed that Akt phosphorylation was inhibited by perifosine in HepG2 and Bel-7402 human hepatocellular carcinoma cells. Perifosine inhibited the growth of HepG2 cells and Bel-7402 cells in a dose-dependent manner, and arrested cell cycle progression at the G(2) phase. Apoptosis induction became more effective with increasing perifosine concentration. The caspase cascade and its downstream effectors, Poly (ADP-ribose) polymerase (PARP), were also activated simultaneously upon perifosine treatment. The proapoptotic effect of perifosine was in part depending on regulation of the phosphorylation level of ERK and JNK. Perifosine cotreatment substantially increased cytotoxic effects of cisplatin in HepG2 cells. Down-regulating the expression of Bcl-2 and up-regulating the level of Bax may be the potential mechanism for this synergistic effect. Our findings suggest that the small molecule Akt inhibitor perifosine shows substantial anti-tumor activity in human hepatoma cancer cell lines, and is a good candidate for treatment combinations with classical cytostatic compounds in hepatocellular carcinoma.
Hong-Rong Fei; Geng Chen; Jian-Mei Wang; Feng-Ze Wang
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Publication Detail:
Type:  Journal Article     Date:  2010-09-15
Journal Detail:
Title:  Cytotechnology     Volume:  62     ISSN:  0920-9069     ISO Abbreviation:  Cytotechnology     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-11-30     Completed Date:  2011-11-10     Revised Date:  2012-05-07    
Medline Journal Info:
Nlm Unique ID:  8807027     Medline TA:  Cytotechnology     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  449-60     Citation Subset:  -    
College of Pharmacology, Taishan Medical University, Chang Cheng Road, Taian, 271016, People's Republic of China.
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