info:eu-repo/semantics/article
6 Iodo-d-lactone: A derivative of arachidonic acid with antitumor effects in HT-29 colon cancer cells
Fecha
2013-04Registro en:
Thomasz, Lisa; Oglio, Andrea Romina; Rossich, Luciano Esteban; Villamar, Sonia; Perona, Marina; et al.; 6 Iodo-d-lactone: A derivative of arachidonic acid with antitumor effects in HT-29 colon cancer cells; Elsevier; Prostaglandins Leukotrienes and Essential Fatty Acids; 88; 4; 4-2013; 273-280
0952-3278
CONICET Digital
CONICET
Autor
Thomasz, Lisa
Oglio, Andrea Romina
Rossich, Luciano Esteban
Villamar, Sonia
Perona, Marina
Salvarredi, Leonardo Andres
Dagrosa, María Alejandra
Pisarev, Mario Alberto
Juvenal, Guillermo Juan
Resumen
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.