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

Dan-Ye Lai1, Yu Chen1, Ting Lan2

  • 1Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, China; Department of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University,China.

Bioorganic Chemistry
|December 4, 2025
PubMed
Abstract

Insights

Gypenoside L from Gynostemma pentaphyllum shows promise against oral cancer by inhibiting the AKT pathway. This natural compound effectively reduced tumor growth in mice with minimal toxicity, suggesting its potential as an oral squamous cell carcinoma treatment.

Area of Science:

  • Oncology
  • Pharmacology
  • Natural Products

Background:

  • Oral squamous cell carcinoma (OSCC) presents significant treatment challenges due to limited efficacy and toxicity.
  • Gynostemma pentaphyllum (JGL), a medicinal herb, exhibits anticancer properties, but its active compounds and mechanisms against OSCC require elucidation.

Purpose of the Study:

  • To identify active compounds from JGL and investigate their therapeutic potential and mechanisms against OSCC.
  • To evaluate the anticancer effects of Gypenoside L (Gyp L) on OSCC cells and in vivo models.

Main Methods:

  • Network pharmacology was employed to screen JGL's active constituents, identifying Gyp L as a key compound targeting the PI3K/AKT pathway.
  • In vitro assays (cell viability, flow cytometry, tumorsphere formation) and in vivo xenograft models were used to assess Gyp L's efficacy.
  • Molecular docking and Western blotting were utilized to explore the underlying molecular mechanisms and pathway activity.

Main Results:

  • Gyp L significantly inhibited OSCC cell proliferation, induced apoptosis, and caused G0/G1 cell cycle arrest.
  • Gyp L demonstrated in vivo anticancer activity by reducing tumor volume in xenograft models without significant systemic toxicity.
  • Mechanistic studies revealed that Gyp L inhibits the AKT signaling pathway by reducing phosphorylated AKT levels.

Conclusions:

  • Gypenoside L is identified as a crucial anticancer component of JGL with therapeutic effects on OSCC.
  • The primary mechanism of Gyp L's action involves the inhibition of the AKT pathway.
  • These findings support the potential of Gyp L as a natural therapeutic agent or adjuvant therapy for oral squamous cell carcinoma.

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