6 Iodo-d-lactone: A derivative of arachidonic acid with antitumor effects in HT-29 colon cancer cells

Abstract

Background: IL-δ (5-hydroxy-6 iodo-8, 11, 14-eicosatrienoic delta lactone) an iodinated arachidonic acid (AA) derivative, is one of the iodolipids biosynthesized by the thyroid. Although IL-δ regulates several thyroid parameters such as cell proliferation and goiter growth it was found that this iodolipid inhibits the growth of other non thyroid cell lines. Objectives: to study the effect of IL-δ on cell proliferation and apoptosis in the colon cancer cell line HT-29. Results: Treatment with IL-δ reduced cell viability in a concentration-dependent manner: 1μM 20%, 5 μM 25%, 10 μM 31 %, 50 μM 47% and caused a significant decrease of PCNA expression (25%). IL-δ had pro-apoptotic effects, evidenced by morphological features of programmed cell death such as: pyknosis, karyorrhexis, cell shrinkage and cell blebbing observed by fluorescence microscopy, an increase in caspase-3 activity and in Bax/Bcl-2 ratio (2.5 after 3 h of treatment). Furthermore, IL-δ increased ROS production (30%) and lipid peroxidation levels (19 %), suggesting that apoptosis could be a result of increased oxidative stress. A maximum increase in c-fos and c-jun protein expression in response to IL-δ was observed 1 h after initiation of the treatment. Treatment with IL-δ blocked HT-29 xenografts growth in nude mice by more than 70% compared with the control group. Conclusion: our study shows that IL-δ inhibits cell growth and induces apoptosis in the colon cancer cell line, HT-29 and opens the possibility that IL-δ could be a potential useful chemotherapy agent.