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A novel agent exerts antitumor activity in breast cancer cells by targeting mitochondrial complex II
Wang L.1; Zhang X.2; Cui G.1; Chan J.Y.-W.1; Wang L.3; Li L.1; Shan L.2; Xu C.2; Zhang Q.1; Wang Y.2; Di L.3; Lee S.M.-Y.1
2016-05-31
Source PublicationOncotarget
ISSN19492553
Volume7Issue:22Pages:32054-32064
Abstract

The mitochondrial respiratory chain, including mitochondrial complex II, has emerged as a potential target for cancer therapy. In the present study, a novel conjugate of danshensu (DSS) and tetramethylpyrazine (TMP), DT-010, was synthesized. Our results showed that DT-010 is more potent than its parental compounds separately or in combination, in inhibiting the proliferation of MCF-7 and MDA-MB-231 cells by inducing cytotoxicity and promoting cell cycle arrest. It also inhibited the growth of 4T1 breast cancer cells in vivo. DT-010 suppressed the fundamental parameters of mitochondrial function in MCF-7 cells, including basal respiration, ATP turnover, maximal respiration. Treatment with DT-010 in MCF-7 and MDA-MB-231 cells resulted in the loss of mitochondrial membrane potential and decreased ATP production. DT-010 also promoted ROS generation, while treatment with ROS scavenger, NAC (N-acetyl-L-cysteine), reversed DT-010-induced cytotoxicity. Further study showed that DT-010 suppressed succinate-induced mitochondrial respiration and impaired mitochondrial complex II enzyme activity indicating that DT-010 may inhibit mitochondrial complex II. Overall, our results suggested that the antitumor activity of DT-010 is associated with inhibition of mitochondrial complex II, which triggers ROS generation and mitochondrial dysfunction in breast cancer cells.

KeywordBreast Cancer Danshensu Mitochondrial Complex Ii Reactive Oxygen Species Tetramethylpyrazine
DOI10.18632/oncotarget.8410
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology ; Cell Biology
WOS SubjectOncology ; Cell Biology
WOS IDWOS:000377748500034
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Cited Times [WOS]:20   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Faculty of Health Sciences
Corresponding AuthorDi L.; Lee S.M.-Y.
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou, China
3.Faculty of Health Sciences, University of Macau, Macao, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationFaculty of Health Sciences;  Institute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Wang L.,Zhang X.,Cui G.,et al. A novel agent exerts antitumor activity in breast cancer cells by targeting mitochondrial complex II[J]. Oncotarget,2016,7(22):32054-32064.
APA Wang L..,Zhang X..,Cui G..,Chan J.Y.-W..,Wang L..,...&Lee S.M.-Y..(2016).A novel agent exerts antitumor activity in breast cancer cells by targeting mitochondrial complex II.Oncotarget,7(22),32054-32064.
MLA Wang L.,et al."A novel agent exerts antitumor activity in breast cancer cells by targeting mitochondrial complex II".Oncotarget 7.22(2016):32054-32064.
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