3-iodothyronamine as a potential anti-tumor compound

Objectives: 3-iodothyronamine (T1AM) is an endogenous messenger chemically related to thyroid hormone, which produces significant effects on energy metabolism and modulates mammalian sirtuin expression. In particular, subchronic T1AM administration was reported to increase the expression of mammalian sirtuin 6 (SIRT6), which has a pro-apoptotic role. Therefore in the present study we evaluated the effects of T1AM on viability and proliferation of cancer and non cancer cell lines. Methods: Four cell lines (HepG2, liver carcinoma; H9c2, cardiomyoblasts; Caco-2, colon carcinoma; and WI-38, lung fibroblasts) were cultured for 24/48h in the presence or absence of different concentrations of exogenous T1AM (0.1-1-10 M). Cell viability was determined by crystal violet staining and transmission electron microscopy (TEM) analysis was performed. To evaluate changes in SIRT 6 gene expression, cells were incubated with the same concentrations of T1AM, and gene expression was assessed by real-time PCR. Results: In HepG2 cells, T1AM significantly reduced cell viability (P<0.05 with 10 M T1AM) while cell proliferation increased in H9c2 and WI-38 cells (P<0.05 with 1-10 M T1AM). After exposure to 10 M T1AM, SIRT6 gene expression increased in HepG2 (p<0.05) while in H9c2 cells it was reduced (p<0.05). No changes were detected in Caco-1 and WI-38 cell lines. TEM analysis revealed morphological changes in mitochondria and endoplasmic reticulum upon 48h of treatment with T1AM (1 M) in either H9c2 or HepG2 cell lines. Nuclear alterations were observed only in HepG2 cells. Conclusion: Our results suggest that T1AM may induce overexpression of SIRT6 and selectively reduce the proliferation of liver cancer cells.