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A novel agent enhances the chemotherapeutic efficacy of doxorubicin in MCF-7 breast cancer cells
Wang L.1; Chan J.Y.1; Zhou X.1; Cui G.1; Yan Z.1; Wang L.2; Yan R.1; Di L.2; Wang Y.3; Hoi M.P.1; Shan L.3; Lee S.M.1
2016-08-10
Source PublicationFrontiers in Pharmacology
ISSN16639812
Volume7Issue:AUG
Abstract

e have previously demonstrated that DT-010, a novel conjugate of danshensu (DSS) and tetramethylpyrazine (TMP), displays anti-tumor effects in breast cancer cells both in vitro and in vivo. In the present study, we investigated whether DT-010 enhances the chemotherapeutic effect of doxorubicin (Dox) in MCF-7 breast cancer cells and exerts concurrent cardioprotective benefit at the same time. Our findings showed that DT-010 was more potent than TMP, DSS, or their combination in potentiating Dox-induced toxicity in MCF-7 cells. Co-treatment with DT-010 and Dox increased apoptosis in MCF-7 cells relative to Dox alone. Further study indicated that glycolytic capacity, glycolytic reserve and lactate level of MCF-7 cells were significantly inhibited after DT-010 treatment. DT-010 also increased the expression of the pro-survival protein GRP78, which was inhibited by co-treatment with Dox. Both endoplasmic reticulum stress inhibitor 4-PBA and knockdown of the expression of GRP78 protein potentiated DT-010-mediated apoptosis in MCF-7 cells. Moreover, DT-010 inhibited Dox-induced cardiotoxicity in H9c2 myoblasts. In conclusion, DT-010 and Dox confer synergistic anti-tumor effect in MCF-7 breast cancer cells through downregulation of the glycolytic pathway and inhibition of the expression of GRP78. Meanwhile, DT-010 also protects against Dox-induced cardiotoxicity.

KeywordBreast Cancer Danshensu Doxorubicin Glycolysis Grp78 Protein Tetramethylpyrazine
DOI10.3389/fphar.2016.00249
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000381346700002
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Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Institute of Chinese Medical Sciences
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.Faculty of Health sciences, University of Macau, Macao, China
3.Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou, China
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Wang L.,Chan J.Y.,Zhou X.,et al. A novel agent enhances the chemotherapeutic efficacy of doxorubicin in MCF-7 breast cancer cells[J]. Frontiers in Pharmacology,2016,7(AUG).
APA Wang L..,Chan J.Y..,Zhou X..,Cui G..,Yan Z..,...&Lee S.M..(2016).A novel agent enhances the chemotherapeutic efficacy of doxorubicin in MCF-7 breast cancer cells.Frontiers in Pharmacology,7(AUG).
MLA Wang L.,et al."A novel agent enhances the chemotherapeutic efficacy of doxorubicin in MCF-7 breast cancer cells".Frontiers in Pharmacology 7.AUG(2016).
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