Butyrate inhibits the mitochondrial complex Ι to mediate mitochondria-dependent apoptosis of cervical cancer cells

doi:10.1186/s12906-023-04043-3

科研成果详情

题名	Butyrate inhibits the mitochondrial complex Ι to mediate mitochondria-dependent apoptosis of cervical cancer cells
作者	Zhang, Ke1; Ji, Xiawei2; Song, Zhengyang1; Song, Wenjing1; Huang, Qunjia 1; Yu, Tiantian 1; Shi, Dibang2; Wang, Fangyan1; Xue, Xiangyang3; Guo, Junping 4
发表日期	2023-06-27
发表期刊	BMC COMPLEMENTARY MEDICINE AND THERAPIES 影响因子和分区
语种	英语
原始文献类型	Article ; Journal Article
关键词	Butyrate Cervical cancer Mitochondria Apoptosis Mitochondrial complex Iota Mitochondrial complex Ι
其他关键词	SODIUM-BUTYRATE ; RISK ; PAPILLOMAVIRUS ; PROLIFERATION ; SUPPRESSES ; ROTENONE
摘要	Background Cervical cancer (CC) is a common gynecological malignancy with high morbidity worldwide. Butyrate, a short-chain fatty acid produced by intestinal flora, has been reported to inhibit cervical carcinogenesis. This study aimed to investigate the pro-apoptotic effects of butyrate on CC and the underlying mechanisms. Methods Human HeLa and Ca Ski cells were used in this study. Cell proliferation, cell migration and invasion were detected by CCK-8 and EdU staining, transwell and wound healing assay, respectively. Cell cycle, mitochondrial membrane potential and apoptosis were evaluated by flow cytometry. Western blot and RT-qPCR were carried out to examine the related genes and proteins to the mitochondrial complex Iota and apoptosis. Metabolite changes were analyzed by energy metabolomics and assay kits. The association between G protein-coupled receptor 41, 43, 109a and CC prognosis was analyzed using data from The Cancer Genome Atlas (TCGA). Results CCK-8 results showed significant inhibition of CC cell proliferation induced by butyrate treatment, which was confirmed by EdU staining and cell cycle detection. Data from the transwell and wound healing assay revealed that CC cell migration was dramatically reduced following butyrate treatment. Additionally, invasiveness was also decreased by butyrate. Western blot analysis showed that cleaved Caspase 3 and cleaved PARP, the enforcers of apoptosis, were increased by butyrate treatment. The results of Annexin V/PI staining and TUNEL also showed an increase in butyrate-induced apoptotic cells. Expression of Cytochrome C (Cytc), Caspase 9, Bax, but not Caspase 12 or 8, were up-regulated under butyrate exposure. Mechanistically, the decrease in mitochondrial NADH and NAD+levels after treatment with butyrate was observed by energy metabolomics and the NAD+/NADH Assay Kit, similar to the effects of the complex Iota inhibitor rotenone. Western blot results also demonstrated that the constituent proteins of mitochondrial complex Iota were reduced by butyrate. Furthermore, mitochondria-dependent apoptosis has been shown to be initiated by inhibition of the complex Iota. Conclusion Collectively, our results revealed that butyrate inhibited the proliferation, migration and invasion of CC cells, and induced mitochondrial-dependent apoptosis by inhibiting mitochondrial complex Iota.
资助项目	Science and Technology Department of Zhejiang [LGF20H070003]; Medical and Health Research Project Grant of Zhejiang Province of China [Y2019317606]; Technology Bureau of Wenzhou [Y2020214, Y20190060]; P&PMed (Shanghai) Biotechnology Co., Ltd.
出版者	BMC
ISSN	2662-7671
EISSN	2662-7671
卷号	23 期号:1
DOI	10.1186/s12906-023-04043-3
页数	14
WOS类目	Integrative & Complementary Medicine
WOS研究方向	Integrative & Complementary Medicine
WOS记录号	WOS:001144913400001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	37370057
SCOPUSEID	2-s2.0-85163767269
通讯作者地址	[Xue, Xiangyang]Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine,Wenzhou Key Laboratory of Cancer-related Pathogens and Immunity,Department of Microbiology and Immunology,Institute of Molecular Virology and Immunology,School of Basic Medical Sciences,Wenzhou Medical University,Wenzhou,325000,China ; [Guo, Junping]Wuyunshan Hospital of Hangzhou,Health Promotion and Research Institute of Hangzhou,Hangzhou,310000,China
Scopus学科分类	Complementary and Alternative Medicine
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/209731
专题	基础医学院（机能实验教学中心）附属第二医院基础医学院（机能实验教学中心）_病原生物学与免疫学系
通讯作者	Xue, Xiangyang; Guo, Junping
作者单位	1.Department of Pathophysiology,School of Basic Medical Science,Wenzhou Medical University,Wenzhou,325000,China; 2.Department of Gastroenterology,The Second Affiliated Hospital,Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,325000,China; 3.Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine,Wenzhou Key Laboratory of Cancer-related Pathogens and Immunity,Department of Microbiology and Immunology,Institute of Molecular Virology and Immunology,School of Basic Medical Sciences,Wenzhou Medical University,Wenzhou,325000,China; 4.Wuyunshan Hospital of Hangzhou,Health Promotion and Research Institute of Hangzhou,Hangzhou,310000,China
第一作者单位	基础医学院（机能实验教学中心）
通讯作者单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系
第一作者的第一单位	基础医学院（机能实验教学中心）
推荐引用方式 GB/T 7714	Zhang, Ke,Ji, Xiawei,Song, Zhengyang,et al. Butyrate inhibits the mitochondrial complex Ι to mediate mitochondria-dependent apoptosis of cervical cancer cells[J]. BMC COMPLEMENTARY MEDICINE AND THERAPIES,2023,23(1).
APA	Zhang, Ke., Ji, Xiawei., Song, Zhengyang., Song, Wenjing., Huang, Qunjia., ... & Guo, Junping. (2023). Butyrate inhibits the mitochondrial complex Ι to mediate mitochondria-dependent apoptosis of cervical cancer cells. BMC COMPLEMENTARY MEDICINE AND THERAPIES, 23(1).
MLA	Zhang, Ke,et al."Butyrate inhibits the mitochondrial complex Ι to mediate mitochondria-dependent apoptosis of cervical cancer cells".BMC COMPLEMENTARY MEDICINE AND THERAPIES 23.1(2023).