Gypenoside L inhibits oral squamous cell carcinoma progression by targeting the AKT signaling pathway.

BACKGROUND: Oral squamous cell carcinoma (OSCC), a prevalent subtype of head and neck squamous cell carcinoma, remains difficult to treat due to limited therapeutic efficacy and high systemic toxicity. Gynostemma pentaphyllum (JGL), a traditional medicinal herb, has demonstrated anticancer potential, but its active constituents and underlying mechanisms against OSCC are not well defined.

METHODS: A network pharmacology approach was used to screen active compounds from JGL. Gypenoside L (Gyp L), a major triterpenoid saponin, was identified as a core bioactive component targeting the PI3K/AKT signaling pathway. Its anticancer effects were validated through cell viability assays, flow cytometry, tumorsphere formation assays, molecular docking, and in vivo xenograft models. Western blotting was performed to evaluate pathway activity.

RESULTS: Gyp L significantly inhibited OSCC cell proliferation, induced apoptosis, and caused G0/G1 cell cycle arrest in vitro. Mechanistically, Gyp L reduced phosphorylated AKT levels without affecting total AKT expression. In vivo, Gyp L treatment effectively reduced tumor volume in xenograft-bearing mice, with no apparent systemic toxicity.

CONCLUSION: Gypenoside L is a key anticancer constituent of JGL, exerting its therapeutic effects in OSCC primarily through inhibition of the AKT pathway. These findings support its potential as a natural therapeutic or adjuvant agent for OSCC.