Apoptotic effects of dichloro stearic and dichloro myristic acid in human hepatoma cells (HepG2).
Chlorinated fatty acids represent the major fraction of extractable organically bound chlorine in fish. After dietary intake such fatty acids may accumulate in adipose tissue, and even be transferred from mother to child via breast milk. We have previously reported that 9,10-dichloro stearic acid and 5,6-dichloro myristic acid inhibited cell growth. The aim of the present work was to investigate whether the growth inhibitory effect of these modified fatty acids might involve apoptosis. Human hepatoma cells (HepG2) were cultured for 4 days before addition of chlorinated fatty acids, and then cultured for another day before harvested. Morphological analysis was mainly done by light microscopy. In addition, fluorescence microscopy and electrophoretic analysis of DNA were carried out. The effect of 0.3 and 0.6 mmol/l was studied. Both chlorinated fatty acids seemed to cause a concentration-dependent increase in the relative abundance of pycnotic and broken nuclei, as well as nuclear fragments, with the strongest effect of dichloro stearic acid. Apoptosis by the chlorinated fatty acids was however less than that of docosahexaenoic acid, a known apoptosis effector. In conclusion, chlorinated fatty acids seem to possess the ability to cause apoptosis.
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Department of Preventive Medicine and Epidemiology, University of Oslo, P.O. Box 1130 Blindern, N-0318 Oslo, Norway.
Høstmark
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Jebens
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D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009227:Myristic Acids / Q000494:pharmacology*; D013229:Stearic Acids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
C400744:5,6-dichloromyristic acid; C114375:9,10-dichlorostearic acid; D004273:DNA, Neoplasm; D009227:Myristic Acids; D013229:Stearic Acids