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Enhancement of Carboplatin- and Quercetin-Induced Cell Death by Roscovitine Is Akt Dependent and p53 Independent in Hepatoma Cells.
MedLine Citation:
PMID:  21994207     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: Hepatocellular carcinoma (HCC) is a common malignancy worldwide and has an annual occurrence of one million new cases. Novel therapeutic strategies of increased efficacy in the treatment of HCC-bearing patients would certainly be helpful. Hence, the authors explored the effect of combination treatment of roscovitine with chemotherapeutic drugs or quercetin (Qctn) in hepatoma cells, HepG2 and Hep3B. METHODS: Cell viability was assessed by MTT assay, cell growth assay, and nuclear morphological changes by DAPI staining. The altered expression of signaling proteins and apoptotic molecules was established by Western blotting. RESULTS: Roscovitine pretreatment considerably enhanced the drugs and Qctn-induced cell death in HepG2 and Hep3B cells. The exploratory studies revealed that augmented cell killing in HepG2 and Hep3B was mediated via Akt pathway and was independent of p53. pAkt was found to be significantly downregulated in combination treatment of roscovitine with carboplatin or Qctn. Corresponding to reduced expression of pAkt, the downstream molecules Bcl-2 and proactive forms of caspase 9 and caspase 3 were also downregulated indicating apoptosis. CONCLUSIONS: The present study reports for the first time, in hepatoma cells, the potentiation of carboplatin- and Qctn-induced cell death by the cell cycle inhibitor roscovitine. Roscovitine can thus be considered as a potential therapeutic target in combination with chemotherapeutic drugs or Qctn for treatment of HCC.
Authors:
Aanchal Sharma; Manoj Kumar Bhat
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-11
Journal Detail:
Title:  Integrative cancer therapies     Volume:  -     ISSN:  1552-695X     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101128834     Medline TA:  Integr Cancer Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
National Centre for Cell Science, Pune, India.
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