br Statistical analysis br All
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.
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AA arachidonic acid
CDK cyclin-dependent kinase
CTU 16( [4-chloro-3-(trifluoromethyl)phenyl]carbamoyl amino)
CYP hexadecanoic acid
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
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
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.
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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
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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.