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  • br Statistical analysis br All

    2020-08-12


    5.2.5. Statistical analysis
    All data are expressed throughout as means ± SEM. Data were analyzed by one-way ANOVA and the Fisher's Partial Least-Squares Difference test was used to detect differences between multiple treat-ments. All experiments were replicated on 3–4 occasions as indicated in figure legends.
    Y. Al-Zubaidi et al.
    Abbreviations
    AA arachidonic acid
    BrdU 5-bromo-2'-deoxyuridine
    CDI N,N‑carbonyldiimidazole
    CDK cyclin-dependent kinase
    CTU 16( [4-chloro-3-(trifluoromethyl)phenyl]carbamoyl amino)
    CYP hexadecanoic acid
    cytochrome P450
    DMEM Dulbecco's Modified Eagle's Medium
    EPA eicosapentaenoic acid
    ESI electrospray ionization
    FBS fetal bovine serum
    HRMS high resolution mass spectrometry
    MAP mitogen-activated protein
    PBS phosphate-buffered saline
    PUFA polyunsaturated fatty acid
    SAR structure-activity relationship
    Author contributions
    Acknowledgements
    This study was supported by grants from the Australian National Health and Medical Research Council (1031686 and 1087248). We are grateful to Prof Christine Clarke of the Westmead Institute for Medical Research (Westmead, NSW, Australia) for the generous gift of MCF10A cells.
    Declarations of interest
    None.
    Appendix A. Supplementary data
    The file contains 1H NMR spectra of all test compounds. Supplementary data related to this article can be found at https://doi.
    References
    Cantrill, E., Murray, M., Mehta, I., Farrell, G.C., 1989. Down-regulation of the male-specific steroid 16α-hydroxylase, cytochrome P-450UT-A, in male rats with portal bypass: relevance to estradiol accumulation and impaired drug metabolism in hepatic cirrhosis. J. Clin. Invest. 83, 1211–1216.
    Cyclin E as a potential therapeutic target in high grade serous ovarian cancer.
    Marcus, C.B., Murray, M., Wilkinson, C.F., 1985. Spectral and inhibitory interactions of methylenedioxyphenyl and related compounds with purified isozymes of cytochrome P-450. Xenobiotica 15, 351–362.
    Mebratu, Y., Tesfaigzi, Y., 2009. How ERK1/2 activation controls cell proliferation and cell death: is subcellular localization the answer? Cell Cycle 8, 1168–1175.
    Y. Al-Zubaidi et al.
    Walker, J.L., Assoian, R.K., 2005. Integrin-dependent signal transduction regulating cy-clin D1 expression and G1-phase AB7FUBAICA progression. Cancer Metastasis Rev. 24, 383–393.
    98 Journal Pre-Proof
    Arylboronate prodrugs of doxorubicin as promising chemotherapy for pancre-atic cancer
    Charles Skarbek, Silvia Serra, Hichem Maslah, Estelle Rascol, Raphaël Labruère
    Please cite this article as: C. Skarbek, S. Serra, H. Maslah, E. Rascol, R. Labruère, Arylboronate prodrugs of
    This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
    JOURNAL PRE-PROOF
    Arylboronate prodrugs of doxorubicin as promising chemotherapy for pancreatic cancer
    Charles Skarbek, Silvia Serra, Hichem Maslah, Estelle Rascol, Raphaël Labruère*
    Institut de Chimie Moléculaire et des Matériaux d’Orsay (ICMMO), CNRS, Univ Paris Sud, Université Paris-Saclay, 15 rue Georges Clemenceau, 91405 Orsay Cedex, France
    Keywords: Prodrug, doxorubicin, reactive oxygen species, anticancer chemotherapy
    * Corresponding author
    E-mail address: [email protected] (R. Labruère).
    Abstract: This study describes the synthesis of arylboronate-based ROS-responsive prodrugs of doxorubicin and their biological evaluation as anticancer agents. The determination of the most sensitive cancer type toward arylboronate prodrugs is crucial for further consideration of these molecules in clinical phase. To address this goal, an arylboronate-based profluorescent probe was used to compare the capacity of various cancer cell lines to efficiently convert the precursor into the free fluorophore. On the selected MiaPaCa-2 pancreatic cancer cells, a benzeneboronate prodrug exhibited 67 % of the cytotoxicity obtained with the free doxorubicin. The prodrug was also able to induce tumor regression on MiaPaCa-2 pancreatic tumor model in ovo. Using this model, the amount of free doxorubicin liberated from this prodrug into the tumor was equivalent to the quantity measured after direct intratumoral injection of the same concentration of doxorubicin.