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  • K 252a br H Beitollahi M Safaei M

    2019-10-21


    [37] H. Beitollahi, M. Safaei, M.R. Shishehbore, S. Tajik, Application of [email protected]/GO nanocomposite for sensitive and selective electrochemical sensing of tryptophan, J. Electrochem. Sci. Eng. 9 (2019) 45–53. [38] S.Z. Mohammadi, H. Beitollahi, S. Tajik, Nonenzymatic coated screen-printed electrode for electrochemical determination of acetylcholine, Micro Nano Syst. Lett. 6 (2018) 9.
    Dan Ou is presently pursuing her master degree in pharmaceutical analysis at Sun Yat-Sen University. Her current research focuses on electrochemical biosensor and its appli-cations in cancer cell research and drug evaluation.
    Duanping Sun received his Ph.D. in pharmaceutical analysis at Sun Yat-Sen University in 2016 under the supervision of Professor Zuanguang Chen. From 2016 to 2018, he worked as a research associate in School of Pharmaceutical Sciences, Sun Yat-Sen K 252a University. Currently, he is employed as an associate professor in Center for Drug Research and Development, Guangdong Pharmaceutical University. His current research interests focus on electrochemical biosensor and cell-based drug screening.
    Zuanguang Chen received his B.S. and Ph.D. in analytical chemistry at Sun Yat-Sen University in 1982 and 2000, respectively. As a professor and director of the Institute of Medical Instrument and Application, School of Pharmaceutical Sciences, Sun Yat-Sen University, his current research interests include analytical instruments, microfluidic system, electrochemical sensor, and pharmaceutical analysis.
    Contents lists available at ScienceDirect
    European Journal of Pharmacology
    journal homepage: www.elsevier.com/locate/ejphar
    Full length article
    A novel derivative of artemisinin inhibits cell proliferation and K 252a T via down-regulation of cathepsin K in breast cancer
    a State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China b Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China
    Keywords:
    Breast cancer
    Testosterone
    Cathepsin K
    Bcl-xL 
    Breast cancer is one of the main diagnosis cancers annually worldwide. It is difficult to thorough cure due to drug resistance and the high possibility of metastasis. SM934 is a novel water-soluble artemisinin analog, and has been reported to have a promising therapeutic effect on multiple autoimmune diseases. In this study, SM934 was combined with Testosterone, which is related to prostate cancer, and the reaction product was SM934-Testosterone. We aimed to explore whether SM934, Testosterone and SM934-Testosterone could inhibit tu-morigenesis and metastasis of breast cancer cells. Moreover, the mechanism also remains to be clarified. The results of our study showed that among the three compounds, only SM934-Testosterone treatment could lead to the suppression of cell proliferation and metastasis with IC50 = 30.66 ± 2.13 μM at 24 h in MDA-MB-231 and IC50 = 31.11 ± 1.79 μM at 24 h in SK-BR-3, where apoptosis was induced. But SM934-Testosterone showed little effects on breast cancer in vivo due to its poor water-solubility. Furthermore, computational target pre-diction and experimental validation demonstrated that Cathepsin K was the target of SM934-Testosterone. SM934-Testosterone inhibited the expression of Cathepsin K in breast cancer cells. Then, down-regulation of Cathepsin K in cancer cells by transfected with Cathepsin K shRNA inhibited cell proliferation and metastasis of breast cancer cells. Moreover, pathway enrichment was performed to understand the mechanism of action that Cathepsin K could adjust apoptosis regulator Bcl-X, and knockdown of Cathepsin K by SM934-Testosterone resulted in the reduction of Bcl-xL, which has been reported to be related to the proliferation and metastasis of cells. Collectively, SM934-Testosterone inhibited proliferation and metastasis ability of breast cancer cells via inhibiting the expression of Cathepsin K followed by the inhibition of Bcl-xL.