Document Detail

The cell cycle effects of docosahexaenoic acid on human metastatic hepatocellular carcinoma proliferation.
MedLine Citation:
PMID:  20198345     Owner:  NLM     Status:  MEDLINE    
Given the reported side effects associated with chemotherapy and surgical resection, dietary intervention with omega-3 polyunsaturated fatty acids (PUFAs) has been postulated to be an alterative way to prevent liver cancer progression and metastasis. We studied the effects of an omega-3 PUFA, docahexaenoic acid (DHA) on COX-2 expression and the cell cycle control machinery that co-ordinately regulate the HCC cells growth. Our data showed that DHA (0-200 microM) retarded proliferation of the human metastatic HCC cell line MHCC97L dose-dependently. In addition, inhibition of cyclin A/Cdk2 interfered with S-phase progression further in agreement with the result of bivariate flow cytometric analysis which indicated that DNA synthesis time (Ts) was significantly prolonged by DHA in MHCC97L. The N-myc oncogene, the heat shock proteins Hsp27 and glucose-related protein 78 (GRP78) as well as the antioxidant enzymes superoxide dismutase may play significant roles in the cell cycle control and reduced-proliferation of MHCC97L by DHA. Our data indicated that it is imperative to develop therapeutic strategy with omega-3 PUFA that simultaneously targets COX-2 and other cell cycle regulators in hepatocarcinogenesis. This study provides novel mechanistic insights into the modulation of DHA on human hepatocarcinoma.
Carol Yee-Ki Lee; Wai-Hung Sit; Sheung-Tat Fan; Kwan Man; Irene Wing-Yan Jor; Leo Lap-Yan Wong; Murphy Lam-Yim Wan; Kian Cheng Tan-Un; Jennifer Man-Fan Wan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  36     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-03     Completed Date:  2010-06-04     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  991-8     Citation Subset:  IM    
School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong, P.R. China.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Carcinoma, Hepatocellular / genetics,  metabolism,  pathology*,  secondary
Cell Adhesion / drug effects
Cell Cycle / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects*
Cyclin A / metabolism
Cyclin E / metabolism
Cyclin-Dependent Kinase 2 / metabolism
Cyclooxygenase 2 / genetics,  metabolism
DNA Replication / drug effects
Docosahexaenoic Acids / pharmacology*
Dose-Response Relationship, Drug
Gene Expression Regulation, Enzymologic / drug effects
Gene Expression Regulation, Neoplastic / drug effects
HSP27 Heat-Shock Proteins / metabolism
Heat-Shock Proteins / metabolism
Liver Neoplasms / genetics,  metabolism,  pathology*
Proto-Oncogene Proteins c-myc / metabolism
RNA, Messenger / metabolism
Superoxide Dismutase / metabolism
Time Factors
Reg. No./Substance:
0/Antineoplastic Agents; 0/Cyclin A; 0/Cyclin E; 0/HSP27 Heat-Shock Proteins; 0/HSPB1 protein, human; 0/Heat-Shock Proteins; 0/Proto-Oncogene Proteins c-myc; 0/RNA, Messenger; 0/molecular chaperone GRP78; 25167-62-8/Docosahexaenoic Acids; EC 2; EC protein, human; EC Dismutase; EC protein, human; EC Kinase 2

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