EGCG and ECG induce apoptosis and decrease autophagy via the AMPK/mTOR and PI3K/AKT/mTOR pathway in human melanoma

Bing-Xin DU1, Pei Lin1, Jun Lin1

  • 1School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China.

Insights

(-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) exhibit antitumor properties by inducing apoptosis and regulating autophagy in melanoma cells. These catechins show potential for human melanoma treatment.

Area of Science:

  • * Oncology
  • * Molecular Biology
  • * Biochemistry

Background:

  • * Catechins possess known antitumor effects, but their precise mechanisms in various cancers remain under investigation.
  • * Human melanoma is a significant health concern, necessitating research into novel therapeutic agents.
  • * (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) are prominent catechins with potential anticancer activities.

Purpose of the Study:

  • * To investigate the effects of EGCG and ECG on human melanoma A375 cells.
  • * To elucidate the underlying molecular mechanisms of EGCG and ECG in melanoma.
  • * To assess the potential of EGCG and ECG as therapeutic agents for melanoma.

Main Methods:

  • * Cell proliferation assays were performed on A375 cells treated with EGCG and ECG.
  • * Flow cytometry was utilized to analyze apoptosis and cell cycle progression.
  • * Protein expression levels of apoptosis-related markers (Bcl-2, Caspase-3), autophagy markers (Beclin-1, LC3, Sirt3), and signaling pathway components (AMPK, PI3K, AKT, mTOR) were assessed.
  • * Mitochondrial membrane potential was measured.

Main Results:

  • * Both EGCG and ECG inhibited A375 cell proliferation, with ECG demonstrating a stronger effect.
  • * EGCG and ECG induced apoptosis and cell cycle arrest, evidenced by altered Bcl-2 and Caspase-3 levels and decreased mitochondrial membrane potential.
  • * Autophagy markers (Beclin-1, LC3, Sirt3) were downregulated, and apoptosis was independent of autophagy modulation.
  • * EGCG and ECG modulated signaling pathways by decreasing p-AMPK and altering p-PI3K/p-AKT/p-mTOR ratios.

Conclusions:

  • * EGCG and ECG induce apoptosis in human melanoma cells through the mitochondrial signaling pathway.
  • * These catechins downregulate autophagy by modulating the AMPK/mTOR and PI3K/AKT/mTOR signaling pathways.
  • * EGCG and ECG demonstrate significant potential for application in human melanoma treatment.

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