Hesperidin Methyl Chalcone Inhibits Hallmarks of Cancer by Targeting the AKT, PI3K/GSK-3β/β-Catenin/STAT3 Signaling Axis in Oral Squamous Cell Carcinoma Models.

Oral squamous cell carcinoma (OSCC) is the most prevalent and drug-resistant cancer. We studied the chemopreventive effects of Hesperidin Methyl Chalcone (HMC) on DMBA-induced hamster buccal pouch carcinogenesis (HBPCs). Male golden Syrian hamsters developed oral tumors on their left buccal pouches after being treated with 0.5% DMBA topically three times a week for 10 weeks. These findings suggest that well-developed squamous cell carcinomas were highly differentiated, exhibiting hyperplasia and dysplasia. Hamsters with DMBA-painted buccal mucosal tissue were treated with HMC, which greatly improved the biochemical and histological changes. In addition, in silico analysis was performed to anticipate possible protein targets for this medication, including Akt, Pi3k, GSk-3β, β-catenin, and STAT3. HMC has a high binding affinity to the above proteins. The current study reveals that HMC has strong chemopreventive properties and protects the Akt, Pi3k, GSk-3β, β-catenin, and STAT3 proteins, which were considerably changed during DMBA-induced oral carcinogenesis.