Tomatidine suppresses PI3K/Akt signaling to induce apoptosis in oral squamous cell carcinoma.
Tomatidine suppresses PI3K/Akt signaling to induce apoptosis in oral squamous cell carcinoma: An in vitro and molecular docking study.
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Abstract
INTRODUCTION: Oral squamous cell carcinoma (OSCC) has high mortality. Over the decades, there has been not substantial improvement in overall survival which is mostly attributed to lack of effective anticancer agent. Tomatidine, a steroidal alkaloid derived and sourced from unripe green tomatoes, has shown immense anticancer potential. However, its activity in OSCC remains largely uncharacterized. This research aims to evaluate the cytotoxic and pro-apoptotic effects of tomatidine in OSCC. METHOD: Target gene for Tomatidine on OSCC treatment was analyzed in the TCGA-HNSC dataset. Two gene were prioritized for network pharmacology to establish their relevance, followed by cheminformatics, drug-target screening, molecular docking, and ADME-T profiling to identify lead compounds. Gene expression and overall survival for target proteins (PI3K/AKT signaling) were examined using GEPIA an cBioportal databases. Functional validation for tomatidine was performed using KB cells via cell viability assay to assess the anticancer effect. RESULTS: Tomatidine treatment reduced the viability of KB cells in a dosage-dependent manner. The docking simulations showed good binding affinities of tomatidine to PI3K (-8.4 kcal/mol), AKT (-8.8), and PTEN (-10.1), suggesting that tomatidine has a potential ability to disrupt PI3K/Akt signaling and apoptosis. CONCLUSION: Tomatidine has potent anticancer effects against OSCC cells inhibiting the PI3K/Akt signaling pathway and promoting apoptosis. These findings highlight the tomatidine utility as a natural anticancer compound.
Affiliation
Sadhana Padmanabhan
External References
- PubMed ID:
- 41487406
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