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Papers by Caroline Barette
Research Square (Research Square), Feb 16, 2021
Xeroderma Pigmentosum protein C (XPC) is involved in recognition and repair of bulky DNA damage s... more Xeroderma Pigmentosum protein C (XPC) is involved in recognition and repair of bulky DNA damage such as lesions induced by Ultra Violet (UV) radiation. XPC-mutated cells are, therefore, photosensitive and accumulate DNA damage leading to increased cancer incidence. Here, we performed a highthroughput screen to identify chemicals capable of normalizing the XP-C phenotype (hyperphotosensitivity and accumulation of photoproducts). Fibroblasts from XP-C patients were treated with a library of approved chemical drugs. Out of 1280 tested chemicals, 16 showed ≥ 25% photo-resistance with RZscore above 2.6 and two drugs were able to favor repair of 6 − 4 pyrimidine pyrimidone photoproducts (6-4PP). Among these two compounds, Isoconazole could partially inhibit apoptosis of the irradiated cells especially when cells were post-treated directly after UV irradiation while Clemizole Hydrochloride-mediated increase in viability was dependent on both pre and post-treatment. No synergistic effect was recorded following combined drug treatment and the compounds exerted no effect on the proliferative capacity of the cells post UV exposure. Amelioration of XP-C phenotype is a pave way towards understanding the accelerated skin cancer initiation in XP-C patients. Further examination is required to decipher the molecular mechanisms targeted by these two chemicals.
International Journal of Molecular Sciences, Oct 13, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
M S-medecine Sciences, Oct 1, 2013
PDF file - 487K, Effects of Pyr1 structural analogues on F-actin organization, on Detyr-microtubu... more PDF file - 487K, Effects of Pyr1 structural analogues on F-actin organization, on Detyr-microtubules generation, and on in cellulo cofilin phosphorylation
MOV file - 6MB, Effect of Pyr1 on microtubule dynamic instability - Time-lapse microscopy after 2... more MOV file - 6MB, Effect of Pyr1 on microtubule dynamic instability - Time-lapse microscopy after 2 hours of incubation, on GFP-EB3 HeLa cells treated with DMSO (control), 5 muM, 10 muM or 25 muM Pyr1, as indicated. 4.Supplementary information
PDF file - 252K, Effect of Pyr1 on NEK11 and MLK1 activity
PDF file - 173K, Characterization of Pyr1 (Pyr1) effects on the inhibition of LIMKs activity in v... more PDF file - 173K, Characterization of Pyr1 (Pyr1) effects on the inhibition of LIMKs activity in vitro
PDF file - 212K, Effect of Pyr1 treatment on the number and on the size of EB1 comets in HeLa cells
PDF file - 173K, Effect of LIMK down regulation on Detyr-tubulin levels
Supplementary Tables 1-3 from Antitumor Activity of Pyridocarbazole and Benzopyridoindole Derivat... more Supplementary Tables 1-3 from Antitumor Activity of Pyridocarbazole and Benzopyridoindole Derivatives that Inhibit Protein Kinase CK2
The alkyloid compound ellipticine derived from the berrywood tree is a topoisomerase II poison th... more The alkyloid compound ellipticine derived from the berrywood tree is a topoisomerase II poison that is used in ovarian and breast cancer treatment. In this study, we report the identification of ellipticine derivatives and their tetracyclic angular benzopyridoindole analogues as novel ATP-competitive inhibitors of the protein kinase CK2. In vitro and in vivo assays showed that these compounds have a good pharmacologic profile, causing a marked inhibition of CK2 activity associated with cell cycle arrest and apoptosis in human cancer cells. Further, in vivo assays demonstrate antitumor activity in a mouse xenograft model of human glioblastoma. Finally, crystal structures of CK2–inhibitor complex provide structural insights on the molecular basis of CK2 inhibition. Our work lays the foundation for development of clinically useful CK2 inhibitors derived from a well-studied scaffold with suitable pharmacokinetics parameters. Cancer Res; 70(23); 9865–74. ©2010 AACR.
Supplementary Figures 1-3 from Antitumor Activity of Pyridocarbazole and Benzopyridoindole Deriva... more Supplementary Figures 1-3 from Antitumor Activity of Pyridocarbazole and Benzopyridoindole Derivatives that Inhibit Protein Kinase CK2
PDF file - 486K, Analysis of the consequence of actin filaments depolymerization on Pyr1 -induced... more PDF file - 486K, Analysis of the consequence of actin filaments depolymerization on Pyr1 -induced formation of Detyr-microtubules
Chemogenomics and Chemical Genetics, 2011
As with all technological platforms for which the number of samples and data exceeds the capacity... more As with all technological platforms for which the number of samples and data exceeds the capacity for human handling, and the activity of which may be of industrial value, it is indispensable to conduct the activity with an ordered mode of functioning, aiming to control and to monitor what takes place.
Plant Physiology, 2018
M.C. performed most of the screening experiments; J.L., M.C., and L.-J.D. contributed to dose-res... more M.C. performed most of the screening experiments; J.L., M.C., and L.-J.D. contributed to dose-response studies and phenotypic analyses; J.L., K.S., and E.M. contributed to whole-genome transcriptomic analyses; V.G. provided technical assistance for lipidomic profiling; F.R. and J.J. provided specific expertise in glycerolipid analyses; C.B. provided specific expertise and technical assistance for phenotypic screens; E.M. conceived the project; all the authors contributed to the writing of the article.
Research Square (Research Square), Feb 16, 2021
Xeroderma Pigmentosum protein C (XPC) is involved in recognition and repair of bulky DNA damage s... more Xeroderma Pigmentosum protein C (XPC) is involved in recognition and repair of bulky DNA damage such as lesions induced by Ultra Violet (UV) radiation. XPC-mutated cells are, therefore, photosensitive and accumulate DNA damage leading to increased cancer incidence. Here, we performed a highthroughput screen to identify chemicals capable of normalizing the XP-C phenotype (hyperphotosensitivity and accumulation of photoproducts). Fibroblasts from XP-C patients were treated with a library of approved chemical drugs. Out of 1280 tested chemicals, 16 showed ≥ 25% photo-resistance with RZscore above 2.6 and two drugs were able to favor repair of 6 − 4 pyrimidine pyrimidone photoproducts (6-4PP). Among these two compounds, Isoconazole could partially inhibit apoptosis of the irradiated cells especially when cells were post-treated directly after UV irradiation while Clemizole Hydrochloride-mediated increase in viability was dependent on both pre and post-treatment. No synergistic effect was recorded following combined drug treatment and the compounds exerted no effect on the proliferative capacity of the cells post UV exposure. Amelioration of XP-C phenotype is a pave way towards understanding the accelerated skin cancer initiation in XP-C patients. Further examination is required to decipher the molecular mechanisms targeted by these two chemicals.
International Journal of Molecular Sciences, Oct 13, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
M S-medecine Sciences, Oct 1, 2013
PDF file - 487K, Effects of Pyr1 structural analogues on F-actin organization, on Detyr-microtubu... more PDF file - 487K, Effects of Pyr1 structural analogues on F-actin organization, on Detyr-microtubules generation, and on in cellulo cofilin phosphorylation
MOV file - 6MB, Effect of Pyr1 on microtubule dynamic instability - Time-lapse microscopy after 2... more MOV file - 6MB, Effect of Pyr1 on microtubule dynamic instability - Time-lapse microscopy after 2 hours of incubation, on GFP-EB3 HeLa cells treated with DMSO (control), 5 muM, 10 muM or 25 muM Pyr1, as indicated. 4.Supplementary information
PDF file - 252K, Effect of Pyr1 on NEK11 and MLK1 activity
PDF file - 173K, Characterization of Pyr1 (Pyr1) effects on the inhibition of LIMKs activity in v... more PDF file - 173K, Characterization of Pyr1 (Pyr1) effects on the inhibition of LIMKs activity in vitro
PDF file - 212K, Effect of Pyr1 treatment on the number and on the size of EB1 comets in HeLa cells
PDF file - 173K, Effect of LIMK down regulation on Detyr-tubulin levels
Supplementary Tables 1-3 from Antitumor Activity of Pyridocarbazole and Benzopyridoindole Derivat... more Supplementary Tables 1-3 from Antitumor Activity of Pyridocarbazole and Benzopyridoindole Derivatives that Inhibit Protein Kinase CK2
The alkyloid compound ellipticine derived from the berrywood tree is a topoisomerase II poison th... more The alkyloid compound ellipticine derived from the berrywood tree is a topoisomerase II poison that is used in ovarian and breast cancer treatment. In this study, we report the identification of ellipticine derivatives and their tetracyclic angular benzopyridoindole analogues as novel ATP-competitive inhibitors of the protein kinase CK2. In vitro and in vivo assays showed that these compounds have a good pharmacologic profile, causing a marked inhibition of CK2 activity associated with cell cycle arrest and apoptosis in human cancer cells. Further, in vivo assays demonstrate antitumor activity in a mouse xenograft model of human glioblastoma. Finally, crystal structures of CK2–inhibitor complex provide structural insights on the molecular basis of CK2 inhibition. Our work lays the foundation for development of clinically useful CK2 inhibitors derived from a well-studied scaffold with suitable pharmacokinetics parameters. Cancer Res; 70(23); 9865–74. ©2010 AACR.
Supplementary Figures 1-3 from Antitumor Activity of Pyridocarbazole and Benzopyridoindole Deriva... more Supplementary Figures 1-3 from Antitumor Activity of Pyridocarbazole and Benzopyridoindole Derivatives that Inhibit Protein Kinase CK2
PDF file - 486K, Analysis of the consequence of actin filaments depolymerization on Pyr1 -induced... more PDF file - 486K, Analysis of the consequence of actin filaments depolymerization on Pyr1 -induced formation of Detyr-microtubules
Chemogenomics and Chemical Genetics, 2011
As with all technological platforms for which the number of samples and data exceeds the capacity... more As with all technological platforms for which the number of samples and data exceeds the capacity for human handling, and the activity of which may be of industrial value, it is indispensable to conduct the activity with an ordered mode of functioning, aiming to control and to monitor what takes place.
Plant Physiology, 2018
M.C. performed most of the screening experiments; J.L., M.C., and L.-J.D. contributed to dose-res... more M.C. performed most of the screening experiments; J.L., M.C., and L.-J.D. contributed to dose-response studies and phenotypic analyses; J.L., K.S., and E.M. contributed to whole-genome transcriptomic analyses; V.G. provided technical assistance for lipidomic profiling; F.R. and J.J. provided specific expertise in glycerolipid analyses; C.B. provided specific expertise and technical assistance for phenotypic screens; E.M. conceived the project; all the authors contributed to the writing of the article.