A novel mechanism of 6-methoxydihydroavicine in suppressing ovarian carcinoma by disrupting mitochondrial homeostasis and triggering ROS/ MAPK mediated apoptosis

doi:10.3389/fphar.2023.1093650

科研成果详情

题名	A novel mechanism of 6-methoxydihydroavicine in suppressing ovarian carcinoma by disrupting mitochondrial homeostasis and triggering ROS/ MAPK mediated apoptosis
作者	Zhang, Huachang 1; Shangguan, Fugen2; Zhang, Lan 3; Ma, Nengfang 4; Song, Shuling 5; Ma, Li 1; Liu, Chuntong 1; Liu, Mengke 1; An, Jing 6; Li, Hua 3; Cao, Qizhi 1
发表日期	2023-05-05
发表期刊	Frontiers in pharmacology 影响因子和分区
语种	英语
原始文献类型	Journal Article ; Article
关键词	6-methoxydihydroavicine (6-ME) MAPK mitochondria homeostasis ovarian cancer (OC) oxaloacetic acid (OAA) metabolism reactive oxygen species (ROS)
其他关键词	CELL-DEATH ; CANCER ; GROWTH
摘要	Introduction: Alkaloids derived from M. cordata (Papaveraceae family), have been found to display antineoplastic activity in several types of cancer. However, the antitumor effects and mechanisms of a new alkaloid extracted from the fruits of M. cordata, named 6-Methoxydihydroavicine (6-ME), remains unclear in the case of ovarian cancer (OC). Methods: CCK-8 assay was employed to analyze the cell viabilities of OC cells. RTCA, and colony-formation assays were performed to measure OC cell growth. Alterations in apoptosis and ROS levels were detected by flow cytometry in accordance with the instructions of corresponding assay kits. A Seahorse XFe96 was executed conducted to confirm the effects of 6-ME on cellular bioenergetics. Western blot and q-RT-PCR were conducted to detect alterations in target proteins. The subcutaneous xenografted tumor model of OC was used to further validate the anti-tumor activity of 6-ME in vivo. Results: Here, we reported for the first time that 6-ME inhibits OC cells growth in vitro and in vivo. Meanwhile, we found that 6-ME showed great antineoplastic activities by disrupting mitochondria homeostasis and promoting apoptosis in OC cells. Further investigation of the upstream signaling of apoptosis revealed that 6-ME-triggered apoptosis was induced by reactive oxygen species (ROS)-mediated mitogen-activated protein kinase (MAPK) activation and mitochondria dysfunction in OC cells. Furthermore, we found oxaloacetic acid (OAA), a crucial metabolite has been proved to be related to NADPH production, can block the cytotoxicity and accumulation of ROS caused by 6-ME in OC cells. Discussion: In summary, our data show that 6-ME exhibits cytotoxicity to OC cells in a ROS-dependent manner by interrupting mitochondrial respiration homeostasis and inducing MAPK-mediated apoptosis. This evidence suggests that 6-ME is a promising remedy for OC intervention
资助项目	Project of Zhejiang Provincial Naturel Science Foundation of China[LQ23H310006];National Natural Science Foundation of China[81672757,82200109];Shandong Provincial Natural Science Foundation[ZR2021LZY024];Science and Technology Bureau of Wenzhou[Y20220171];Youth Innovation and Technology Support Program in Colleges and Universities of Shandong Province[2022KJ090];
出版者	FRONTIERS MEDIA SA
ISSN	1663-9812
EISSN	1663-9812
卷号	14
DOI	10.3389/fphar.2023.1093650
页数	15
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001000416100001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
Pubmed记录号	37214469
Scopus记录号	2-s2.0-85159865199
通讯作者地址	[Cao, Qizhi]Department of Immunology,School of Basic Medical Sciences,Binzhou Medical University,Shandong,Yantai,China ; [Li, Hua]The Affiliated Taian City Central Hospital of Qingdao University,Shandong,Taian,China
scopus学科分类	Pharmacology;Pharmacology (medical)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/180542
专题	第一临床医学院（信息与工程学院）、附属第一医院_浙江省胰脏肝脏危重性疾病重点实验室附属第一医院
通讯作者	Li, Hua; Cao, Qizhi
作者单位	1.Department of Immunology,School of Basic Medical Sciences,Binzhou Medical University,Shandong,Yantai,China; 2.Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 3.The Affiliated Taian City Central Hospital of Qingdao University,Shandong,Taian,China; 4.School of Life and Environmental Sciences,Wenzhou University,Wenzhou,China; 5.School of Gerontology,Binzhou Medical University,Shandong,Yantai,China; 6.Division of Infectious Diseases and Global Health,School of Medicine,University of California San Diego (UCSD),La Jolla,CA,United States
推荐引用方式 GB/T 7714	Zhang, Huachang,Shangguan, Fugen,Zhang, Lan,et al. A novel mechanism of 6-methoxydihydroavicine in suppressing ovarian carcinoma by disrupting mitochondrial homeostasis and triggering ROS/ MAPK mediated apoptosis[J]. Frontiers in pharmacology,2023,14.
APA	Zhang, Huachang., Shangguan, Fugen., Zhang, Lan., Ma, Nengfang., Song, Shuling., ... & Cao, Qizhi. (2023). A novel mechanism of 6-methoxydihydroavicine in suppressing ovarian carcinoma by disrupting mitochondrial homeostasis and triggering ROS/ MAPK mediated apoptosis. Frontiers in pharmacology, 14.
MLA	Zhang, Huachang,et al."A novel mechanism of 6-methoxydihydroavicine in suppressing ovarian carcinoma by disrupting mitochondrial homeostasis and triggering ROS/ MAPK mediated apoptosis".Frontiers in pharmacology 14(2023).