title: Uptake of 3-iodothyronamine hormone analogs inhibits the growth and viability of cancer cells.
abstract: 3-Iodothyronamine (T1AM) is a structural analog of thyroid hormone that has been demonstrated to have potent affects on numerous physiological systems. Most studies on T1AM have explored its effects in healthy functional systems; while its potential therapeutic uses and safety, and efficacy in pathological conditions are largely unknown. We sought to evaluate the effects of T1AM and its structural analog SG-2 on cancer cell growth and viability. We analyzed the cytotoxicity of these analogs on MCF7 breast cancer cells, HepG2 hepatocellular cancer cells as well as normal control cells using primary human foreskin fibroblasts and mouse preadipocytes control cells. The cytotoxicity of T1AM and SG-2 was determined by cell growth curves, and validated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assays. Cellular uptake analysis was conducted using confocal microscopy. Real-time (RT)-PCR was conducted to identify gene pathways affected by SG-2 in cancer cells. The IC50of T1AM was approximately double the concentration of its analog SG-2 in cancer cells. Cytotoxicity studies on normal cells revealed that IC50concentrations of SG-2 in cancer cells had no significant impact on cell viability in these cell types. Cell-imaging experiments demonstrated rapid uptake and localization to the mitochondrial membrane. T1AM and SG-2 are able to reduce cancer cell growth and viability. These findings support the potential for use of these compounds and related analogs for their antiproliferation properties in cancer cells.
authors.affiliation: Department of Nutritional Sciences Texas Tech University Lubbock TX USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Rogowski
authors.affiliation: Department of Biological Sciences Texas Tech University Lubbock TX USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Gollahon
authors.affiliation: Department of Biochemistry University of Wisconsin-Madison WI USA.
authors.forename: Grazia
authors.initials: G
authors.lastname: Chellini
authors.affiliation: Department of Zoology University of Wisconsin-Madison WI USA; Magnetic Resonance Facility at Madison WI USA.
authors.forename: Fariba M
authors.initials: FM
authors.lastname: Assadi-Porter
keywords: 3‐Iodothyronamine; 3‐Iodothyronamine synthetic analog; SG‐2; T1AM; cancer; metabolic substrate utilization