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.
Abstract:
Catechins have been proven to exert antitumor effects in different kinds of cancers. However, the underlying mechanisms have not been completely clarified yet. This study aimed to assess the effects and mechanisms of (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) on human melanoma skin A375 cells. Results showed that EGCG and ECG inhibited the proliferation of A375 cells and ECG showed better inhibitory effect. Flow cytometry analysis had shown that EGCG and ECG induced apoptosis and led to cell cycle arrest. EGCG and ECG decreased Bcl-2 expression and upregulated Caspase-3 protein level, indicating the development of apoptosis. Furthermore, EGCG and ECG could decreased mitochondrial membrane potential of A375 cells. In addition, the expression of Beclin-1, LC3 and Sirt3 were downregulated at protein levels, which known to be associated with autophagy. After autophagy was increased by rapamycin, the apoptotic trend was not change, indicating that apoptosis and autophagy are independent. Mechanistically, EGCG and ECG treatments decreased phosphorylated-AMPK (p-AMPK) and increased the ratios of p-PI3K, p-AKT and p-mTOR in melanoma cells. Conclusively, EGCG and ECG induced apoptosis via mitochondrial signaling pathway, downregulated autophagy through modulating the AMPK/mTOR and PI3K/AKT/mTOR signaling pathway. It indicated that EGCG and ECG may be utilized in human melanoma treatment.
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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