Apoptotic Effects of Dichloro Stearic and Dichloro Myristic Acid in Human Hepatoma Cells (HepG2)

Abstract

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.

Distribution and pharmacokinetics of double-radiolabeled endotoxin in the rat brain and peripheral organs

“…This is believed to be involved in aging and in many human diseases, including cancer (Ames, 1989). There is also increasing evidence showing the involvement of unsaturated fatty acids in the cell death pathways, particularly in the context of apoptotic signaling (Lystad et al, 2001;Zhu et al, 2005). Our study suggests that an active involvement of fatty acids moiety of lipid A in the endotoxin inflammation process in the brain.…”

Distribution of androstenedione and its effects on total free fatty acids in pregnant rats

“…There is increasing evidence showing the involvement of unsaturated fatty acids in cell death pathways, particularly in the context of apoptotic signaling. Polyunsaturated FFAs have been shown to be apoptotic in liver and brain (Lystad et al, 2001, Zhu et al, 2005 Apoptosis may participate in a wide variety of disease processes, but its mechanistic and functional relationship to these conditions remain incompletely understood (Kadenbach et al, 2004).…”

“…In a separate study, oleic acid has produced concentrationand time-dependent damage with typical apoptotic features in cortical and hippocampal cultures from embryonic and neonatal rats, respectively, as well as in human neuroblastoma SH-SY5Y cells (Zhu et al, 2005). Cultured human hepatoma cells (HepG2) in the presence of chlorinated stearic acid also produced a concentration-dependent increase in the relative abundance of broken nuclei, as a sign of apoptosis (Lystad et al, 2001). Authors claimed that the effect of chlorinated stearic acid was, however, less than that of docosahexaenoic acid (DHA), a known apoptosis effector.…”