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Inhibition of STX17-SNAP29-VAMP8 complex formation by costunolide sensitizes ovarian cancer cells to cisplatin via the AMPK/mTOR signaling pathway

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资源类型：
Pubmed体系：
作者：
Liang Xiao[1] ; Yu Chunlei[2] ; Tian Yunhong[3] ; Xiang Xiaocong[1,4,*1] ; Luo Yuexi[5] ;
机构： [1]Institute of Hepato-Biliary-Pancreatic-Intestinal Disease, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China [2]Institute of Materia Medica, School of Pharmacy, North Sichuan Medical College, Nanchong 637000, China [3]Department of General Surgery, The Second Clinical Medical College, North Sichuan Medical College, Nanchong 637000, China [4]Institute of Tissue Engineering and Stem Cells, North Sichuan Medical College, Nanchong 637000, China [5]Department of Obstetrics, The Second Clinical Medical College, North Sichuan Medical College, Nanchong 637000, China
出处：
DOI： 10.1016/j.bcp.2023.115549
ISSN：

关键词： Costunolide Autophagy Lysosome Cisplatin Ovarian cancer

摘要：
Ovarian cancer (OC) is the most common gynecological malignancy. Chemotherapy failure is a major challenge in OC treatment. Targeting autophagy is a promising strategy to enhance the cytotoxicity of chemotherapeutic agents. In this study, we found that costunolide (CTD) inhibits autophagic flux and exhibits high therapeutic efficacy for OC treatment in an in vitro model. Mechanistically, CTD inactivates AMPK/mTOR signaling to inhibit autophagy initiation at the early stage and blocks mTORC1-dependent autophagosome-lysosome fusion at the late stage during autophagy by disrupting SNARE complex (STX17-SNAP29-VAMP8) formation, resulting in lethal autophagy arrest in OC cells. Furthermore, CTD sensitizes OC cells to cisplatin (CDDP) by blocking CDDP-induced autophagy both in vitro and in vivo. Together, our data provide novel mechanistic insights into CTD-induced autophagy arrest and suggest a new autophagy inhibitor for effective treatment of OC.Copyright © 2023 Elsevier Inc. All rights reserved.

基金：
National Natural Science Foundation of China Youth Project (81903026); the Sichuan Science and Technology Program (20YYJC2624); the Ministry of Education “Chunhui Plan” cooperative scientific research project (12); the Bureau of Science and Technology and Intellectual Property of Nanchong (22SXJCQN0003, 22JCYJPT0007, and 20SXQT0307); the Scientific Research Project of the Health Commission of Sichuan Province (21PJ192); and the Medical scientific research Project of Sichuan Province (S21025 and Q21002).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 2 区 医学
小类 | 2 区 药学
最新[2023]版：
大类 | 2 区 医学
小类 | 2 区 药学
第一作者：
第一作者机构： [1]Institute of Hepato-Biliary-Pancreatic-Intestinal Disease, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
通讯作者：
通讯机构： [1]Institute of Hepato-Biliary-Pancreatic-Intestinal Disease, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China [4]Institute of Tissue Engineering and Stem Cells, North Sichuan Medical College, Nanchong 637000, China [*1]Institute of Hepato-Biliary-Pancreatic-Intestinal Disease, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China
推荐引用方式(GB/T 7714)：
Liang Xiao,Yu Chunlei,Tian Yunhong,et al.Inhibition of STX17-SNAP29-VAMP8 complex formation by costunolide sensitizes ovarian cancer cells to cisplatin via the AMPK/mTOR signaling pathway[J].Biochemical pharmacology.2023,212:115549.doi:10.1016/j.bcp.2023.115549.
APA：
Liang Xiao,Yu Chunlei,Tian Yunhong,Xiang Xiaocong&Luo Yuexi.(2023).Inhibition of STX17-SNAP29-VAMP8 complex formation by costunolide sensitizes ovarian cancer cells to cisplatin via the AMPK/mTOR signaling pathway.Biochemical pharmacology,212,
MLA：
Liang Xiao,et al."Inhibition of STX17-SNAP29-VAMP8 complex formation by costunolide sensitizes ovarian cancer cells to cisplatin via the AMPK/mTOR signaling pathway".Biochemical pharmacology 212.(2023):115549

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