PMID- 34729107 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211105 IS - 1837-9664 (Print) IS - 1837-9664 (Electronic) IS - 1837-9664 (Linking) VI - 12 IP - 23 DP - 2021 TI - Anticancer Effects of Helminthostachys zeylanica Ethyl acetate Extracts on Human Gastric Cancer Cells through Downregulation of the TNF-alpha-activated COX-2-cPLA2-PGE(2) Pathway. PG - 7052-7068 LID - 10.7150/jca.64638 [doi] AB - 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-alpha (TNF-alpha)-activated proinflammatory cytosolic phospholipase A2 (cPLA2)-COX-2-prostaglandin E(2) (PGE(2)) pathway. Conclusions: Our results suggest that H. zeylanica-E2 has potential as a novel adjunctive agent for the treatment of GC. CI - (c) The author(s). FAU - Tsai, Ming-Ming AU - Tsai MM AD - 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. FAU - Lin, Horng-Chyuan AU - Lin HC AD - Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Yu, Ming-Chin AU - Yu MC AD - Department of Surgery, New Taipei Municipal TuCheng Hospital, Chang Gung Memorial Hospital at Linkou, and College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Lin, Wan-Jung AU - Lin WJ AD - 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. FAU - Chu, Mei-Yi AU - Chu MY AD - 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. FAU - Tsai, Ching-Ching AU - Tsai CC AD - 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. FAU - Cheng, Ching-Yi AU - Cheng CY AD - 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. AD - Department of Pulmonary Infection and Immunology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. LA - eng PT - Journal Article DEP - 20211017 PL - Australia TA - J Cancer JT - Journal of Cancer JID - 101535920 PMC - PMC8558661 OTO - NOTNLM OT - Helminthostachys zeylanica OT - anti-inflammation OT - anticancer OT - gastric cancer COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2021/11/04 06:00 MHDA- 2021/11/04 06:01 PMCR- 2021/01/01 CRDT- 2021/11/03 06:56 PHST- 2021/07/06 00:00 [received] PHST- 2021/09/24 00:00 [accepted] PHST- 2021/11/03 06:56 [entrez] PHST- 2021/11/04 06:00 [pubmed] PHST- 2021/11/04 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - jcav12p7052 [pii] AID - 10.7150/jca.64638 [doi] PST - epublish SO - J Cancer. 2021 Oct 17;12(23):7052-7068. doi: 10.7150/jca.64638. eCollection 2021.