Raddeanin A promotes the apoptosis of gastric cancer in conjunction with autophagy inhibitor Hydroxychloroquine via MAPK signaling pathway

IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Journal of Traditional and Complementary Medicine Pub Date : 2024-07-20 DOI:10.1016/j.jtcme.2024.07.004
Yuhao Teng , Ying Xing , Weiwei Xue , Yue Hu , Zirui Li , Jun Qian , Ruiping Wang
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Abstract

Purpose

Gastric cancer (GC) is among the malignant cancers with the highest incidence and mortality worldwide. As GC is not very sensitive to current chemotherapy drugs, there is an urgent need to develop new effective drugs. Raddeanin A (RA) is extracted from the traditional Chinese medicine Anemone raddeana Regel, which has an anti-cancer effect. The purpose of this study was to explore the effects of RA on GC in vitro and in vivo.

Methods

We explored the targets of RA in GC through network pharmacology. MTT assay, flow cytometry, Western blotting, and other methods were used to detect the effects of RA on the proliferation, apoptosis, and autophagy of GC cells. After preconditioning with hydroxychloroquine (HCQ) and rapamycin, we observed the effects of RA-induced autophagy on apoptosis. We further verified the antitumor effect and safety of RA in vivo. Using SNU-1 xenograft tumor model in nude mice, tumor volume was observed and liver toxicity was observed by immunohistochemistry.

Results

Many cancer-related signaling pathways were visualized using Cytoscape software. Among them, the MAPK signaling pathway was one of the highest-ranked pathways. The MTT assay results suggested that RA could inhibit the proliferation of HGC-27 and SNU-1 cells effectively. Flow cytometry and Western blotting confirmed that RA could significantly induce apoptosis of HGC-27 and SNU-1 cells. Electron microscopy and Western blotting demonstrated that RA could induce autophagy of HGC-27 and SNU-1 cells. Further experiments suggested that HCQ, an autophagy inhibitor, could enhance the capacity of RA to induce apoptosis. In animal studies, we found that intraperitoneal injection of RA could effectively and safely inhibit gastric tumors.

Conclusions

RA significantly inhibited the proliferation and induced autophagy and apoptosis of GC cells. In combination with HCQ, RA-induced apoptosis increased in vitro. The combined application of RA and autophagy inhibitors may serve as an added approach to the treatment of GC, but the underlying mechanism needs further exploration. In vivo, it was observed that RA has a good antitumor effect without increasing liver toxicity.

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Raddeanin A 与自噬抑制剂羟氯喹通过 MAPK 信号通路共同促进胃癌细胞凋亡
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来源期刊
Journal of Traditional and Complementary Medicine
Journal of Traditional and Complementary Medicine Medicine-Complementary and Alternative Medicine
CiteScore
9.30
自引率
6.70%
发文量
78
审稿时长
66 days
期刊介绍: eJTCM is committed to publish research providing the biological and clinical grounds for using Traditional and Complementary Medical treatments as well as studies that demonstrate the pathophysiological and molecular/biochemical bases supporting the effectiveness of such treatments. Review articles are by invitation only. eJTCM is receiving an increasing amount of submission, and we need to adopt more stringent criteria to select the articles that can be considered for peer review. Note that eJTCM is striving to increase the quality and medical relevance of the publications.
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