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

Background: IL-delta (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-delta 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-delta on cell proliferation and apoptosis in the colon cancer cell line HT-29. Results: Treatment with IL-delta reduced cell viability in a concentration-dependent manner: 1 mu M 20%, 5 mu M 25%, 10 mu M 31%, 50 mu M 47% and caused a significant decrease of PCNA expression (25%). IL-delta 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, and an increase in caspase-3 activity and in Bax/Bcl-2 ratio (2.5 after 3 h of treatment). Furthermore, IL-delta 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-delta was observed 1 h after initiation of the treatment IL-delta also induced a tumour growth delay of 70% compared to the control group in NIH nude mice implanted with HT-29 cells. Conclusion: Our study shows that IL-delta inhibits cell growth and induces apoptosis in the colon cancer cell line, HT-29 and opens the possibility that IL-delta could be a potential useful chemotherapy agent. (c) 2013 Elsevier Ltd. All rights reserved.