Curcumin downregulates the <scp>PI3K–AKT–mTOR</scp> pathway and inhibits growth and progression in head and neck cancer cells
Gabriel Álvares Borges, Silvia Taveira Elias, Bruna Rabelo Amorim, Caroline Lourenço de Lima, Ricardo D. Coletta, Rogério M. Castilho, Cristiane H. Squarize, Eliete Neves Silva Guerra
Abstract
Abstract Curcumin, a polyphenol isolated from the rhizome of Curcuma longa , has been studied because of its antioxidant, antimicrobial, and antiinflammatory properties. This study aimed to evaluate the effects of curcumin on head and neck cancer (HNC) cell lines and how it modulates the PI3K–AKT–mTOR signaling pathway. Dose‐response curves for curcumin were established for hypopharynx carcinoma (FaDu), tongue carcinoma (SCC‐9), and keratinocytes (HaCaT) cell lines and IC 50 values were calculated. Cell cycle and cell death were investigated through flow cytometry. Cytoskeleton organization was assessed through phalloidin+FITC staining. qPCR array and western blot were performed to analyze gene and protein expression. Curcumin reduced cell viability in a dose‐dependent and selective manner, induced cell death on SCC‐9 cells (necrosis/late apoptosis: 44% curcumin vs. 16.4% vehicle), and arrested cell cycle at phase G 2 /M on SCC‐9 and FaDu (G 2 : SCC‐9—19.1% curcumin vs. 13.4% vehicle; FaDu—37.8% curcumin vs. 12.9% vehicle). Disorganized cytoskeleton and altered cell morphology were observed. Furthermore, curcumin downregulated the PI3K–AKT–mTOR signaling pathway by modifying the expression of key genes and proteins. These findings highlight the promising therapeutic potential of curcumin to inhibit HNC growth and progression and to modulate the PI3K–AKT–mTOR pathway.