The curcumin analogue PAC has potent anti-anaplastic thyroid cancer effects

Abstract

Anaplastic thyroid carcinoma (ATC) is the rarest type of thyroid cancer, but is the common cause of death from these tumors. The aggressive behavior of ATC makes it resistant to the conventional therapeutic approaches. Thus, the present study was designed to evaluate the anti-ATC efficacy of the piperidone analogue of curcumin (PAC). We have shown that PAC induces apoptosis in thyroid cancer cells in a time-dependent fashion through the mitochondrial pathway. Immunoblotting analysis revealed that PAC suppressed the epithelial-to-mesenchymal transition (EMT) process in ATC cells by upregulating the epithelial marker E-cadherin and reducing the level of the mesenchymal markers N-cadherin, Snail, and Twist1. This anti-EMT effect was confirmed by showing PAC-dependent inhibition of the proliferation and migration abilities of ATC cells. Furthermore, PAC inhibited the AKT/mTOR pathway in ATC cells. Indeed, PAC downregulated mTOR and its downstream effectors p70S6K and 4E-BP1 more efficiently than the well-known mTOR inhibitor rapamycin. In addition to the promising in vitro anticancer efficacy, PAC significantly suppressed the growth of humanized thyroid tumor xenografts in mice. Together, these findings indicate that PAC could be considered as promising therapeutic agent for anaplastic thyroid carcinomas.