An induction of Retinol Binding Protein 4 by new platinum-based
anticancer agent LA-12

a 2011

An induction of Retinol Binding Protein 4 by new platinum-based anticancer agent LA-12

STRUHÁROVÁ, Iva, Pavel BOUCHAL, Jiří JARKOVSKÝ, Kristýna HRAZDILOVÁ, Monika DVOŘÁKOVÁ et. al.

Basic information

Original name

An induction of Retinol Binding Protein 4 by new platinum-based anticancer agent LA-12

Authors

STRUHÁROVÁ, Iva, Pavel BOUCHAL, Jiří JARKOVSKÝ, Kristýna HRAZDILOVÁ, Monika DVOŘÁKOVÁ, Lenka HERNYCHOVÁ, Jiří DAMBORSKÝ, Petr SOVA and Bořivoj VOJTĚŠEK

Edition

"2nd RECAMO joint meeting": Role of p53, MDM2, AGR2/3 and ubiquitin/chaperone system in tumour biology, 2011

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

10600 1.6 Biological sciences

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Science

ISBN

978-80-86793-20-7

Keywords in English

proteomics, LA-12, RBP4

Abstract

V originále

Cisplatin belongs to the most widely used platin-based agent used in cancer chemotherapy. However, its use is rather limited mainly due to its severe side effects and resistance (either congenital or acquired). Therefore there has been an effort made to develop a new generation of platin-based drugs. In our work, we studied the biological properties of a new anticancer agent (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12). We followed the initial pharmacokinetic study by measuring proteomic profiles of rat plasma to identify new LA-12 target proteins which could potentially serve as markers of LA-12 treatment, response and therapy monitoring. Using a proteomic approach based on surface-enhanced laser desorption-ionization time-of-flight mass spectrometry we measured proteomic profiles of 72 samples of rat plasma characterized by one of four LA-12 doses and one of six time intervals (since rat dosage). Correlation of 92 peak clusters with platinum concentration was evaluated. We identified plasma retinol binding protein RBP4 as a protein correlating with LA-12 level in both rat plasma and plasma ultrafiltrate. The level of RBP4 was also determined in plasma of patients from LA-12 clinical evaluation by western blotting and the similar trend was shown. Molecular modeling of the RBP4/LA-12 complex was performed to investigate the potential functional cooperation of RBP4 in LA-12 transport. We described an induction of RBP4 by a new platinum-based anticancer drug LA-12 in both rat and human plasma. The induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anticancer drugs. Cisplatin belongs to the most widely used platin-based agent used in cancer chemotherapy. However, its use is rather limited mainly due to its severe side effects and resistance (either congenital or acquired). Therefore there has been an effort made to develop a new generation of platin-based drugs. In our work, we studied the biological properties of a new anticancer agent (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12). We followed the initial pharmacokinetic study by measuring proteomic profiles of rat plasma to identify new LA-12 target proteins which could potentially serve as markers of LA-12 treatment, response and therapy monitoring. Using a proteomic approach based on surface-enhanced laser desorption-ionization time-of-flight mass spectrometry we measured proteomic profiles of 72 samples of rat plasma characterized by one of four LA-12 doses and one of six time intervals (since rat dosage). Correlation of 92 peak clusters with platinum concentration was evaluated. We identified plasma retinol binding protein RBP4 as a protein correlating with LA-12 level in both rat plasma and plasma ultrafiltrate. The level of RBP4 was also determined in plasma of patients from LA-12 clinical evaluation by western blotting and the similar trend was shown. Molecular modeling of the RBP4/LA-12 complex was performed to investigate the potential functional cooperation of RBP4 in LA-12 transport. We described an induction of RBP4 by a new platinum-based anticancer drug LA-12 in both rat and human plasma. The induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anticancer drugs.

Links

GAP304/10/0868, research and development project

Name: Studium molekulárních mechanismů časného metastazování do lymfatických uzlin u karcinomu prsu nízkého stupně malignity pomocí proteomických technik

Investor: Czech Science Foundation

MZ0MOU2005, plan (intention)

Name: Funkční diagnostika zhoubných nádorů

Citovat

STRUHÁROVÁ, Iva, Pavel BOUCHAL, Jiří JARKOVSKÝ, Kristýna HRAZDILOVÁ, Monika DVOŘÁKOVÁ, Lenka HERNYCHOVÁ, Jiří DAMBORSKÝ, Petr SOVA and Bořivoj VOJTĚŠEK. An induction of Retinol Binding Protein 4 by new platinum-based anticancer agent LA-12. In "2nd RECAMO joint meeting": Role of p53, MDM2, AGR2/3 and ubiquitin/chaperone system in tumour biology. 2011. ISBN 978-80-86793-20-7.

@proceedings{960200,
   author = {Struhárová, Iva and Bouchal, Pavel and Jarkovský, Jiří and Hrazdilová, Kristýna and Dvořáková, Monika and Hernychová, Lenka and Damborský, Jiří and Sova, Petr and Vojtěšek, Bořivoj},
   booktitle = {"2nd RECAMO joint meeting": Role of p53, MDM2, AGR2/3 and ubiquitin/chaperone system in tumour biology},
   keywords = {proteomics, LA-12, RBP4},
   language = {eng},
   isbn = {978-80-86793-20-7},
   title = {An induction of Retinol Binding Protein 4 by new platinum-based anticancer agent LA-12},
   year = {2011}
}

TY  - CONF
ID  - 960200
AU  - Struhárová, Iva - Bouchal, Pavel - Jarkovský, Jiří - Hrazdilová, Kristýna - Dvořáková, Monika - Hernychová, Lenka - Damborský, Jiří - Sova, Petr - Vojtěšek, Bořivoj
PY  - 2011
TI  - An induction of Retinol Binding Protein 4 by new platinum-based anticancer agent LA-12
SN  - 9788086793207
KW  - proteomics, LA-12, RBP4
N2  - Cisplatin belongs to the most widely used platin-based agent used in cancer chemotherapy. However, its use is rather limited mainly due to its severe side effects and resistance (either congenital or acquired). Therefore there has been an effort made to develop a new generation of platin-based drugs. In our work, we studied the biological properties of a new anticancer agent (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12). We followed the initial pharmacokinetic study by measuring proteomic profiles of rat plasma to identify new LA-12 target proteins which could potentially serve as markers of LA-12 treatment, response and therapy monitoring. Using a proteomic approach based on surface-enhanced laser desorption-ionization time-of-flight mass spectrometry we measured proteomic profiles of 72 samples of rat plasma characterized by one of four LA-12 doses and one of six time intervals (since rat dosage). Correlation of 92 peak clusters with platinum concentration was evaluated. We identified plasma retinol binding protein RBP4 as a protein correlating with LA-12 level in both rat plasma and plasma ultrafiltrate. The level of RBP4 was also determined in plasma of patients from LA-12 clinical evaluation by western blotting and the similar trend was shown. Molecular modeling of the RBP4/LA-12 complex was performed to investigate the potential functional cooperation of RBP4 in LA-12 transport. We described an induction of RBP4 by a new platinum-based anticancer drug LA-12 in both rat and human plasma. The induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anticancer drugs. Cisplatin belongs to the most widely used platin-based agent used in cancer chemotherapy. However, its use is rather limited mainly due to its severe side effects and resistance (either congenital or acquired). Therefore there has been an effort made to develop a new generation of platin-based drugs. In our work, we studied the biological properties of a new anticancer agent (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12). We followed the initial pharmacokinetic study by measuring proteomic profiles of rat plasma to identify new LA-12 target proteins which could potentially serve as markers of LA-12 treatment, response and therapy monitoring. Using a proteomic approach based on surface-enhanced laser desorption-ionization time-of-flight mass spectrometry we measured proteomic profiles of 72 samples of rat plasma characterized by one of four LA-12 doses and one of six time intervals (since rat dosage). Correlation of 92 peak clusters with platinum concentration was evaluated. We identified plasma retinol binding protein RBP4 as a protein correlating with LA-12 level in both rat plasma and plasma ultrafiltrate. The level of RBP4 was also determined in plasma of patients from LA-12 clinical evaluation by western blotting and the similar trend was shown. Molecular modeling of the RBP4/LA-12 complex was performed to investigate the potential functional cooperation of RBP4 in LA-12 transport. We described an induction of RBP4 by a new platinum-based anticancer drug LA-12 in both rat and human plasma. The induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anticancer drugs.
ER  -

STRUHÁROVÁ, Iva, Pavel BOUCHAL, Jiří JARKOVSKÝ, Kristýna HRAZDILOVÁ, Monika DVOŘÁKOVÁ, Lenka HERNYCHOVÁ, Jiří DAMBORSKÝ, Petr SOVA and Bořivoj VOJTĚŠEK. An induction of Retinol Binding Protein 4 by new platinum-based anticancer agent LA-12. In \textit{''2nd RECAMO joint meeting'': Role of p53, MDM2, AGR2/3 and ubiquitin/chaperone system in tumour biology}. 2011. ISBN~978-80-86793-20-7.

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