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.

The Effects of Tetrahydrocurcumin on Adriamycin and Taxane resistance in Anaplastic Thyroid Cancer Cells

“…They concluded that this ineffectiveness is due to MDR1 and BCRP expressions. Some potent curcumin analogues, i.e., PAC (piperidone analogue of curcumin), are capable of inhibiting EMT/CSC pathways and Akt/mTOR signaling simultaneously (54). The major limitation of the present study is the lack of analysis of the expression patterns of MDR proteins within the CSC subgroup of ATC cells.…”

Curcuminoids as Anticancer Drugs: Pleiotropic Effects, Potential for Metabolic Reprogramming and Prospects for the Future

“…The way curcumin analogs boost the efficacy of anti-immune checkpoint inhibitors also represents a new research field under development [ 30 ]. Finally, among the 25 recently reviewed curcumin analogs [ 15 ], at least eight have been the subject of continuous investigations with respect to their pleiotropic anticancer effects, in 2023 alone [ 254 , 255 , 256 , 257 , 258 , 259 , 260 , 261 ]. As these molecules may overcome limitations of bioavailability and pharmacokinetics that were recently reviewed based on clinical data [ 17 ], the hope is that the current research might soon lead to clinical trials involving cancer patients for at least some of them.…”

Multifaceted physiological and therapeutical impact of curcumin on hormone‐related endocrine dysfunctions: A comprehensive review

“…PAC induced apoptosis, suppressed the epithelial‐to‐mesenchymal transition process, and targeted the AKT/mTOR pathway in ATC cells. In vivo studies further supported the potential of PAC as a therapeutic agent for anaplastic thyroid carcinomas (Al‐Mohanna et al, 2023). Metastasis, a critical aspect of thyroid cancer aggressiveness, prompted investigations into the potential of Cur to suppress metastatic steps.…”

“…T A B L E 3 (Continued) (Zhang, Qiu, et al, 2023) In vivo studies further supported the potential of PAC as a therapeutic agent for anaplastic thyroid carcinomas (Al-Mohanna et al, 2023).…”

“…Anaplastic thyroid cancer (ATC), renowned for its aggressiveness, faced the therapeutic impact of Cur and deguelin, suppressing cancer stem‐cell properties and profoundly altering aggressive behavior (Al‐Mohanna et al, 2023; Kocdor et al, 2019). Additionally, another study explored the anti‐ATC efficacy of a piperidone analog of Cur (PAC).…”