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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. To study the effect of IL-δ on cell proliferation and apoptosis in the colon cancer cell line HT-29. Treatment with IL-δ reduced cell viability in a concentration-dependent manner: 1μM 20%, 5μM 25%, 10μM 31%, 50μM 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, and an increase in caspase-3 activity and in Bax/Bcl-2 ratio (2.5 after 3h 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 1h after initiation of the treatment. IL-δ also induced a tumour growth delay of 70% compared to the control group in NIH nude mice implanted with HT-29 cells. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Citation

Lisa Thomasz, Romina Oglio, Luciano Rossich, Sonia Villamar, Marina Perona, Leonardo Salvarredi, Alejandra Dagrosa, Mario A Pisarev, Guillermo J Juvenal. 6 Iodo-δ-lactone: a derivative of arachidonic acid with antitumor effects in HT-29 colon cancer cells. Prostaglandins, leukotrienes, and essential fatty acids. 2013 Apr;88(4):273-80

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PMID: 23375358

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