Deciphering the Mechanism of Curcumin-induced Apoptosis in Human Laryngeal Cancer: Involvement of MiRNA-203-Mediated Survivin Downregulation and Activation of the Mitochondrial Pathway

A BSTRACT Background: Laryngeal cancer treatment options have been investigated using anticancer curcumin (CUR). Modifying particular miRNAs, such as miR-203, can reduce the growth of laryngeal cancer cells and increase apoptosis. Laryngeal cancer cells usually have miR-203 downregulated, which is an antitumor miRNA. It targets survivin, a protein essential for cell survival and apoptosis resistance. MiR-203 enhances apoptosis by preventing the inactivation of caspase-3 and caspase-7, which are essential for the apoptotic process. This is accomplished by suppressing the production of survivin. Methodology: Curcumin (CUR) therapy caused apoptosis in a human laryngeal cancer cell line (HEP2), according to a study. This was supported by the concentration-dependent rise in cell viability and mitochondrial membrane potential (MMP), as well as the considerable uptick in levels of the apoptosis-related genes Bax and Caspase-3. Cells treated with CUR also showed morphological alterations linked to apoptotic cell death, such as membrane blebbing, chromatin condensation, and nuclear disintegration. The study design was an in vitro experimental study. The cytotoxic potential of CUR was evaluated in HEP-2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay across a concentration range (1.56-100 μg/mL) at 24, 48, and 72 h. MMP disruption was assessed using JC-1 staining, whereas nuclear morphological changes were visualized by 4’,6-diamidino-2-phenylindole (DAPI) staining. Apoptotic induction was quantified using Annexin V-FITC/PI dual staining and analyzed by flow cytometry. Furthermore, reverse transcription-quantitative polymerase chain reaction was performed to determine the expression of apoptosis-related genes and miRNA-203, with normalization against reference controls. Results and Conclusion: These results imply that CUR upregulates miR-203 and targets survivin in HEP2 cells to enhance mitochondria-mediated apoptosis. Therefore, CUR may be a promising therapeutic agent with advantages over current therapies for the treatment of resistant laryngeal cancer. However, more investigation and clinical studies are required to confirm these results and fully examine the benefits of CUR in laryngeal.