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A novel agent attenuates cardiotoxicity and improves antitumor activity of doxorubicin in breast cancer cells
Ying Zhang1; Hongkuan Deng2; Hefeng Zhou1; Yucong Lu1; Luchen Shan3; Simon Ming‐Yuen Lee4; Guozhen Cui1
2019-04
Source PublicationJOURNAL OF CELLULAR BIOCHEMISTRY
ISSN0730-2312
Volume120Issue:4Pages:5913-5922
Abstract

Doxorubicin (Dox) is a well‐known chemotherapeutic agent used in the treatment of various cancers. However, Dox‐induced cardiotoxicity limits its further clinical use. We have previously reported a small molecular named biotin‐conjugated ADTM analog (BAA) that exhibits cytoprotective effects against oxidative stress–induced cell injury in cardiomyoblast H9c2 cells. Here, the protective effects of BAA, indexed by attenuation of the cardiotoxicity induced by Dox as well as synergistic antitumor activity that increases the chemotherapeutic efficacy of Dox were investigated. Our results demonstrated that BAA significantly ameliorated Dox‐induced toxicity in the H9c2 cells and zebrafish models. In addition, BAA attenuated Dox‐induced endoplasmic reticulum (ER) stress in H9c2 cells. An ER stress inhibitor, 4‐phenylbutyric acid, reversed the protective effect of BAA in H9c2 cells. In contrast, in human breast tumor MDA‐MB‐231 cells, BAA significantly enhanced Dox‐induced cytotoxicity through upregulating Dox‐induced ER stress response. Taken together, our findings indicate that Dox combined with BAA can significantly enhance its antitumor activity in breast cancer cells and reduce its cardiotoxicity, at least in part, by mediating ER stress activation.

KeywordAntitumor Biotin-conjugated Adtm Analog (Baa) Cardioprotection Cardiotoxicity Doxorubicin (Dox)
DOI10.1002/jcb.27880
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000459010100117
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Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai, China
2.Department of Pharmaceutical Engineering, School of Life Sciences, Shandong University of Technology, Zibo, China
3.Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio‐cerebrovascular Diseases, Jinan University College of Pharmacy, Guangzhou, China
4.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China
Recommended Citation
GB/T 7714
Ying Zhang,Hongkuan Deng,Hefeng Zhou,et al. A novel agent attenuates cardiotoxicity and improves antitumor activity of doxorubicin in breast cancer cells[J]. JOURNAL OF CELLULAR BIOCHEMISTRY,2019,120(4):5913-5922.
APA Ying Zhang.,Hongkuan Deng.,Hefeng Zhou.,Yucong Lu.,Luchen Shan.,...&Guozhen Cui.(2019).A novel agent attenuates cardiotoxicity and improves antitumor activity of doxorubicin in breast cancer cells.JOURNAL OF CELLULAR BIOCHEMISTRY,120(4),5913-5922.
MLA Ying Zhang,et al."A novel agent attenuates cardiotoxicity and improves antitumor activity of doxorubicin in breast cancer cells".JOURNAL OF CELLULAR BIOCHEMISTRY 120.4(2019):5913-5922.
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