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

• Published in: Prostaglandins, leukotrienes and essential fatty acids Vol. 88; no. 4; pp. 273 - 280
• Main Authors: Thomasz, Lisa, Oglio, Romina, Rossich, Luciano, Villamar, Sonia, Perona, Marina, Salvarredi, Leonardo, Dagrosa, Alejandra, Pisarev, Mario A, Juvenal, Guillermo J
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.04.2013
• Subjects: Advanced Basic Science; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Arachidonic acid; Arachidonic Acid - chemistry; Arachidonic Acids - chemistry; Arachidonic Acids - pharmacology; Cell Proliferation - drug effects; Colon cancer; Endocrinology & Metabolism; HT29 Cells; Humans; Iodolactone; Iodolipids; Thyroid; Iodolipids; Iodolactone; Colon cancer; Arachidonic acid; Thyroid
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1016/j.plefa.2013.01.002

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: 1 μM 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, and 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. IL-δ 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-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.