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 IC 50 of T1AM was approximately double the concentration of its analog SG‐2 in cancer cells. Cytotoxicity studies on normal cells revealed that IC 50 concentrations 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.
Highlights
3-Iodothyronamine (T1AM) is a structural analog of thyroid hormone that has been demonstrated to have potent affects on numerous physiological systems
Cytotoxicity studies on normal cells revealed that inhibitory concentration 50% (IC50) concentrations of SG-2 in cancer cells had no significant impact on cell viability in these cell types
Our results showed that incubation of MCF7 cells with T1AM and SG-2 over 72 h resulted in significant
Summary
3-Iodothyronamine (T1AM) is a structural analog of thyroid hormone that has been demonstrated to have potent affects on numerous physiological systems. 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. More recent research has demonstrated a promising application for T1AM to potentially treat obesity, causing weight loss by shifting macronutrient metabolism away from carbohydrates towards oxidation of fatty acids [9,10]. These shifts in macronutrient substrate utilization are supported by recent findings that chronic T1AM administration induces transcriptional activation changes consistent with a more lipolytic metabolic pattern [11]. This shift moves toward a more metabolically healthy state in the obese condition as excess lipid is mobilized for energy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
