Anticancer Effects of Helminthostachys zeylanica Ethyl acetate Extracts on Human Gastric Cancer Cells through Downregulation of the TNF-α-activated COX-2-cPLA2-PGE2 Pathway

泽兰长穗竹乙酸乙酯提取物通过下调 TNF-α 激活的 COX-2-cPLA2-PGE2 通路对人胃癌细胞发挥抗癌作用

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作者:Ming-Ming Tsai, Horng-Chyuan Lin, Ming-Chin Yu, Wan-Jung Lin, Mei-Yi Chu, Ching-Ching Tsai, Ching-Yi Cheng

Background

Gastric cancer (GC) is the second most prevalent cancer worldwide and the eighth most common cause of tumor-related death in Taiwan. Helminthostachys zeylanica, a flavonoid compound, has anti-inflammatory, immunomodulatory, and anticancer effects. We examined whether an extract of H. zeylanica (E1 and E2) has potential as a treatment for GC.

Conclusions

Our results suggest that H. zeylanica-E2 has potential as a novel adjunctive agent for the treatment of GC.

Methods

We investigated the effects (pro-apoptosis, pro-autophagy, and antiproliferation ability) of H. zeylanica-E2 on cell viability in healthy gastric epithelial (GES-1) and GC cells (AGS and BGC823). H. zeylanica-E2 was toxic to GC cells but had little or no toxicity to normal cells.

Results

In this study, H. zeylanica-E2 induced apoptosis through caspase 3/7, Bcl-2, Bax, cyclooxygenase-2 (COX-2), and cleaved poly (ADP-ribose) polymerase pathways in GC cells. In addition, it increased autophagy by stimulating autophagy-related protein (ATG)5, ATG7, LC3-I/LC3-II, and inhibiting COX-2 activity in GC cells. We also found that H. zeylanica-E2 exhibited antiproliferation ability through cell cycle arrest in G0/G1 and G2/M and suppressed the migration of GC cells. The anticancer effects of H. zeylanica-E2 in GC cells might be mediated partly through inhibition of tumor necrosis factor-α (TNF-α)-activated proinflammatory cytosolic phospholipase A2 (cPLA2)-COX-2-prostaglandin E2 (PGE2) pathway. Conclusions: Our results suggest that H. zeylanica-E2 has potential as a novel adjunctive agent for the treatment of GC.

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