Cancer Management and Research (May 2020)
Active Monomer RTR-1 Derived from the Root of Rhodomyrtus tomentosa Induces Apoptosis in Gastric Carcinoma Cells by Inducing ER Stress and Inhibiting the STAT3 Signaling Pathway
Abstract
Xiangqiang Zhang,1,* Jinxia Cheng,1,* Peiyan He,2 Jinyan Zhu,3 Zhixian Chen,2 Shenyu Miao,4 Guocai Wang,5 Jianwei Jiang,2 Yuechun Wang1 1Department of Physiology, Basic Medical College, Jinan University, Guangzhou 510630, People’s Republic of China; 2Department of Biochemistry, Basic Medical College, Jinan University, Guangzhou 510630, People’s Republic of China; 3Department of Immunology, Basic Medical College, Jinan University, Guangzhou 510630, People’s Republic of China; 4School of Life Sciences, Guangzhou University, Guangzhou, People’s Republic of China; 5Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianwei JiangDepartment of Biochemistry, Basic Medical College, Jinan University, Guangzhou 510630, People’s Republic of ChinaEmail [email protected] WangDepartment of Physiology, Basic Medical College, Jinan University, Guangzhou 510630, People’s Republic of ChinaEmail [email protected]: Rhodomyrtus tomentosa, a flowering plant from the Myrtaceae family, is considered an antitumour substance with versatile biological and pharmacological activities. RTR-1 is an active monomer purified from the root of Rhodomyrtus tomentosa. However, the detail of mechanism involving in RTR-1 anti-cancer activity remains to be elucidated, and the effect on gastric cancer cells is unknown.Methods: Cell proliferation was determined by MTT and clone formation assay. The effect of RTR-1 on cell cycle distribution and apoptosis was analysed utilizing flow cytometry, respectively. Moreover, Western blotting was used to detect the expression of cell cycle- and apoptosis-related protein.Results: Based on MTT and clone formation assay, we noticed that RTR-1 inhibited the proliferation of gastric carcinoma (BGC823 and SGC7901) cells in a dose- and time-dependent manner. Furthermore, the results of flow cytometry and Western blotting showed that RTR-1 induced cell cycle arrest in the G2/M phase through the ATM-Chk2-p53-p21 signaling pathway and induced cell apoptosis by inhibiting the signal transducers and activators of transcription 3 (STAT3) pathway and activating the endoplasmic reticulum stress (ER stress) pathway.Conclusion: Taken together, these results demonstrate that RTR-1 induces cell cycle arrest and promotes apoptosis in gastric carcinoma, indicating its potential application for gastric cancer therapy.Keywords: RTR-1, gastric carcinoma cells, cell cycle, apoptosis, ER stress, STAT3
