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
Received 4 November 2019
Accepted for publication 6 March 2020
Published 5 May 2020 Volume 2020:12 Pages 3117—3129
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Kenan Onel
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 work
Correspondence: Jianwei Jiang
Department of Biochemistry, Basic Medical College, Jinan University, Guangzhou 510630, People’s Republic of China
Department of Physiology, Basic Medical College, Jinan University, Guangzhou 510630, People’s Republic of China
Purpose: 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
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