Exploring betanin regulatory impact on TGF-β and PI3K/AKT pathways in oral cancer

Oral squamous cell carcinoma (OSCC) presents ongoing clinical difficulties due to its frequent recurrence and unfavorable prognosis. Betanin (BTN) is recognized for its potent antioxidant and anticancer properties; however, its specific molecular mechanisms, particularly those related to the apoptotic and TGF-β/PI3K-Akt signalling pathways, remain partially unexplored. An in vivo study was performed using 7,12-dimethylbenz[a]anthracene (DMBA)-induced OSCC in hamsters, where the expression patterns of PI3K, Akt, Bax, Bcl-2, Caspase-3, Caspase-9, mutant p53, TGF-β RI & RII, SMAD-2, SMAD-4, and SMAD-7 were examined through immunohistochemistry, Western blot, and qRT-PCR, with a focus on PI3K/Akt and TGF-β signaling pathways. BTN, administered in vivo, attenuated tumor progression in OSCC-afflicted hamsters in a dose-dependent manner, inhibiting growth-regulatory signalling nodes such as PI3K, Akt, Bcl-2, mutant p53, TGF-β RI, TGF-β RII, SMAD-2, and SMAD-4, while promoting the expression of apoptotic proteins SMAD-7, Bax, Caspase-3, and Caspase-9. BTN exhibits multi-targeted anticancer potential in OSCC by modulating the expression of with key apoptotic (Bax, Bcl-2, Caspases-3 & 9, mutant p53) and growth-regulatory signalling nodes PI3K, Akt, TGF-β RI, TGF-β RII, SMAD-2, 4, and 7. Our previous molecular docking study directly engages the aforementioned proteins. As a result, the current experimental framework identifies BTN as a potential chemopreventive agent, meriting additional mechanistic and therapeutic research in the context of oral cancer.