Active Monomer RTR-1 Derived from the Root of Rhodomyrtus t omentosa Induces Apoptosis in Gastric Carcinoma Cells by Inducing ER Stress and Inhibiting the STAT3 Signaling Pathway

从桃金娘根部提取的活性单体RTR-1通过诱导内质网应激和抑制STAT3信号通路诱导胃癌细胞凋亡。

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Abstract

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.

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