Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 37 GP27.04 | DOI: 10.1530/endoabs.37.GP.27.04

ECE2015 Guided Posters Thyroid – hyperthyroidism and treatment (8 abstracts)

TIM16 inhibition enhances sensitivity to paclitaxel and decreases calcitonin secretion by reducing mitochondrial membrane potential in a human medullary thyroid carcinoma cell line

Teresa Gagliano 1 , Eleonora Riva 1 , Federico Tagliati 1 , Daniele Matteotti 1 , Valentina Brugnoli 1 , Silvia Sambugaro 1 , Marta Bondanelli 1 , Erica Gentilin 1 , Simona Falletta 1 , Katiuscia Benfini 1 , Carmelina Di Pasquale 1 , Remo Guerrini 2 , Severo Salvadori 2 , Ettore degli Uberti 1 & Maria Chiara Zatelli 1

1Section of Endocrinology and Internal Medicine, Department of Medical Science, University of Ferrara, Ferrara, Italy; 2Department of Chemical and Pharmaceutical, University of Ferrara, Ferrara, Italy.

TIM16, a protein of the translocase complex TIM23 of the mitochondrial inner membrane, is encoded by the Magmas a gene. Magmas silencing has been associated with a greater sensitivity to apoptotic stimuli in pituitary adenoma cell lines. We recently demonstrated that in a human medullary thyroid carcinoma cell line (TT) compound 5, a TIM16 inhibitor, was not cytotoxic but enhanced the proapoptotic effects of staurosporine. The aim of our study is to verify whether mithocondrial function is involved in compound 5 effects. To evaluate cell viability we performed ATPlite assay, while caspase 3/7 assay was used to determine apoptotic activation. ELISA test was used for calcitonin detection in cell culture medium, while TMRM assay was employed to evaluate mitochondrial membrane potential (MMP). Our data show that paclitaxel 10 nM was reduced cell viability by 40%, while compound 5 alone had no effects. However, compound 5 was able to significantly increase the effects of paclitaxel by nearly 14%. In addition, paclitaxel increased caspase 3/7 activity by 130%, which was further increased by co-incubation with compound 5. In addition, we found that compound 5 was able to reduce basal and pentagastrin induced calcitonin secretion. Furthermore, compound 5 and paclitaxel decreased MMP (by −15 and −20% vs CT respectively), and their combination was even more potent (−50% vs CT). In conclusion, compound 5 could represent a tool to increase the effects of chemotherapeutic agents and to control hypercalcitoninemia in medullary thyroid carcinoma.

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