title: A Novel Agent Enhances the Chemotherapeutic Efficacy of Doxorubicin in MCF-7 Breast Cancer Cells.
abstract: We 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.
authors: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau Macao, China.
authors: Liang
authors: L
authors: Wang
authors: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau Macao, China.
authors: Judy Y
authors: JY
authors: Chan
authors: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau Macao, China.
authors: Xinhua
authors: X
authors: Zhou
authors: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau Macao, China.
authors: Guozhen
authors: G
authors: Cui
authors: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau Macao, China.
authors: Zhixiang
authors: Z
authors: Yan
authors: Faculty of Health sciences, University of Macau Macao, China.
authors: Li
authors: L
authors: Wang
authors: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau Macao, China.
authors: Ru
authors: R
authors: Yan
authors: Faculty of Health sciences, University of Macau Macao, China.
authors: Lijun
authors: L
authors: Di
authors: Institute of New Drug Research, College of Pharmacy, Jinan University Guangzhou, China.
authors: Yuqiang
authors: Y
authors: Wang
authors: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau Macao, China.
authors: Maggie P
authors: MP
authors: Hoi
authors: Institute of New Drug Research, College of Pharmacy, Jinan University Guangzhou, China.
authors: Luchen
authors: L
authors: Shan
authors: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau Macao, China.
authors: Simon M
authors: SM
authors: Lee
keywords: GRP78 protein; breast cancer; danshensu; doxorubicin; glycolysis; tetramethylpyrazine