The cell cycle effects of docosahexaenoic acid on human metastatic hepatocellular carcinoma proliferation

Carol Yee-Ki Lee, Wai-Hung Sit, Sheung-Tat Fan, Kwan Man, Irene Wing-Yan Jor, Leo Lap-Yan Wong, Murphy Wan, Kian Cheng Tan-Un, Jennifer Man-Fan Wan

Research output: Contribution to journalArticlepeer-review


Given the reported side effects associated with chemotherapy and surgical resection, dietary intervention with ω-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 ω-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 µM) 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 ω-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.
Original languageEnglish
Pages (from-to)991-998
Number of pages8
JournalInternational Journal of Oncology
Issue number4
Publication statusPublished - 1 Apr 2010


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