PMID- 36245270 OWN - NLM STAT- MEDLINE DCOM- 20230222 LR - 20230222 IS - 1099-1573 (Electronic) IS - 0951-418X (Linking) VI - 37 IP - 2 DP - 2023 Feb TI - Chinese dragon's blood ethyl acetate extract suppresses gastric cancer progression through induction of apoptosis and autophagy mediated by activation of MAPK and downregulation of the mTOR-Beclin1 signalling cascade. PG - 689-701 LID - 10.1002/ptr.7652 [doi] AB - Gastric cancer (GC) is a malignancy with high morbidity and mortality. Chinese dragon's blood is a traditional Chinese medicine derived from the red resin of Dracaena cochinchinensis (Lour.) S. C. Chen. However, the antigastric cancer effect of Chinese dragon's blood has not yet been reported. Herein, we demonstrated that Chinese dragon's blood ethyl acetate extract (CDBEE) suppressed the proliferative and metastatic potential of human gastric cancer MGC-803 and HGC-27 cells. CDBEE suppressed epithelial-mesenchymal transition in MGC-803 and HGC-27 cells. Moreover, CDBEE induced apoptotic and autophagic cell death in MGC-803 and HGC-27 cells. The cytotoxicity of CDBEE in human gastric epithelial GES-1 cells was dramatically weaker than that in human gastric cancer cells. Mechanistically, the activation of the mitogen-activated protein kinase (MAPK) signalling pathway was involved in the growth inhibition of MGC-803 and HGC-27 cells by CDBEE. Additionally, CDBEE-induced autophagic cell death was mediated by downregulation of the mammalian target of rapamycin (mTOR)-Beclin1 signalling cascade and upregulation of the ATG3/ATG7-LC3 signalling cascade. Importantly, CDBEE exhibited potent anti-GC efficacy in vivo without obvious toxicity or side effects. Therefore, CDBEE may be a promising candidate drug for the treatment of gastric cancer, especially for GC patients with aberrant MAPK signalling or mTOR signalling. CI - (c) 2022 John Wiley & Sons Ltd. FAU - Ouyang, Lishan AU - Ouyang L AUID- ORCID: 0000-0002-2912-5339 AD - Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Li, Jiaqi AU - Li J AD - Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Chen, Xiaonan AU - Chen X AD - Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Huang, Huiming AU - Huang H AD - Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Tian, Yingying AU - Tian Y AD - Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Li, Xingxing AU - Li X AUID- ORCID: 0000-0002-8096-5106 AD - Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. FAU - Pang, Daoran AU - Pang D AD - Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. AD - Innovation Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Wei, Xuejiao AU - Wei X AD - Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Xie, Jinxin AU - Xie J AD - Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Wang, Longyan AU - Wang L AD - Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Liu, Dongxiao AU - Liu D AD - Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Tu, Pengfei AU - Tu P AD - Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Li, Jun AU - Li J AD - Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Hu, Zhongdong AU - Hu Z AUID- ORCID: 0000-0003-4849-3353 AD - Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. LA - eng GR - 82030114/National Natural Science Foundation of China/ GR - 82074072/National Natural Science Foundation of China/ GR - Z191100001119083/Beijing Nova Program of Science and Technology/ PT - Journal Article DEP - 20221017 PL - England TA - Phytother Res JT - Phytotherapy research : PTR JID - 8904486 RN - M3YJ2C28IC (dragon's blood) RN - 76845O8NMZ (ethyl acetate) RN - 0 (Beclin-1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - W36ZG6FT64 (Sirolimus) RN - 0 (Plant Extracts) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.1.1 (MTOR protein, human) RN - Dracaena cochinchinensis SB - IM MH - Humans MH - *Stomach Neoplasms/drug therapy MH - Beclin-1/metabolism MH - Mitogen-Activated Protein Kinases/metabolism MH - Sirolimus MH - Down-Regulation MH - Plant Extracts/pharmacology/metabolism MH - *Dracaena/metabolism MH - TOR Serine-Threonine Kinases/metabolism MH - Apoptosis MH - Autophagy OTO - NOTNLM OT - Chinese dragon's blood OT - MAPK OT - apoptosis OT - autophagy OT - gastric cancer OT - mTOR EDAT- 2022/10/18 06:00 MHDA- 2023/02/22 06:00 CRDT- 2022/10/17 03:33 PHST- 2022/07/24 00:00 [revised] PHST- 2022/06/20 00:00 [received] PHST- 2022/08/02 00:00 [accepted] PHST- 2022/10/18 06:00 [pubmed] PHST- 2023/02/22 06:00 [medline] PHST- 2022/10/17 03:33 [entrez] AID - 10.1002/ptr.7652 [doi] PST - ppublish SO - Phytother Res. 2023 Feb;37(2):689-701. doi: 10.1002/ptr.7652. Epub 2022 Oct 17.