J Cancer 2021; 12(23):7052-7068. doi:10.7150/jca.64638 This issue

Research Paper

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

Ming-Ming Tsai1*, Horng-Chyuan Lin2*, Ming-Chin Yu3, Wan-Jung Lin4, Mei-Yi Chu4, Ching-Ching Tsai5, Ching-Yi Cheng4,6✉

1. Department of Nursing, Division of Basic Medical Sciences, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan and Department of General Surgery, Chang Gung Memorial Hospital at Chiayi, Chiayi, Taiwan.
2. Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
3. Department of Surgery, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital at Linkou, and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
4. Graduate Institute of Health Industry Technology, Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
5. Department of Nursing, College of Nursing, Chang Gung University of Science and Technology, and Department of Cardiology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
6. Department of Pulmonary Infection and Immunology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
*These authors have contributed equally to this work.

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Citation:
Tsai MM, Lin HC, Yu MC, Lin WJ, Chu MY, Tsai CC, Cheng CY. 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. J Cancer 2021; 12(23):7052-7068. doi:10.7150/jca.64638. Available from https://www.jcancer.org/v12p7052.htm

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Abstract

Graphic abstract

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.

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.

Keywords: Helminthostachys zeylanica, anti-inflammation, anticancer, gastric cancer