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L-Canavanine potentiates the cytotoxicity of doxorubicin and cisplatin in arginine deprived human cancer cells

The non-protein amino acid L-canavanine (L-CAV), an antimetabolite of L-arginine (L-ARG), can alter the 3D conformation of proteins when incorporated into a protein instead of L-ARG. L-CAV inhibits the proliferation of some tumour cells. The deprivation of L-ARG in the culture medium enhances the re...

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Autores principales: Nurcahyanti, Agustina DR, Wink, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734457/
https://www.ncbi.nlm.nih.gov/pubmed/26839743
http://dx.doi.org/10.7717/peerj.1542
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author Nurcahyanti, Agustina DR
Wink, Michael
author_facet Nurcahyanti, Agustina DR
Wink, Michael
author_sort Nurcahyanti, Agustina DR
collection PubMed
description The non-protein amino acid L-canavanine (L-CAV), an antimetabolite of L-arginine (L-ARG), can alter the 3D conformation of proteins when incorporated into a protein instead of L-ARG. L-CAV inhibits the proliferation of some tumour cells. The deprivation of L-ARG in the culture medium enhances the response of cells to L-CAV. This study aimed to investigate the interaction of L-CAV in combination with the chemotherapeutic drugs, doxorubicin (DOX) or cisplatin (CIS), in cancer cells, especially in the absence of L-ARG. A combination method based on the median-effect principle and mass-action law was used. The following cancer cells were employed: HeLa and Caco-2 cells, overexpressing argininosuccinate synthase (ASS), pancreatic cells (MIA PaCa-2 and BxPC-3) and hepatocellular carcinoma cells (Hep G2 and SK-HEP-1), with down-regulated ASS. When constant and non-constant ratios of L-CAV were combined with DOX and CIS, a synergistic potentiation of cytotoxicity was recorded. Cells expressing high levels of ASS were more sensitive to the treatment as compared to the cells with reduced ASS levels. Overall, this study may provide a new approach to targeting some cancer cells with L-CAV in combination with DNA-targeting drugs such as DOX and CIS, especially those cells which overexpress ASS, such as human cervical and colorectal carcinoma cells.
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spelling pubmed-47344572016-02-02 L-Canavanine potentiates the cytotoxicity of doxorubicin and cisplatin in arginine deprived human cancer cells Nurcahyanti, Agustina DR Wink, Michael PeerJ Oncology The non-protein amino acid L-canavanine (L-CAV), an antimetabolite of L-arginine (L-ARG), can alter the 3D conformation of proteins when incorporated into a protein instead of L-ARG. L-CAV inhibits the proliferation of some tumour cells. The deprivation of L-ARG in the culture medium enhances the response of cells to L-CAV. This study aimed to investigate the interaction of L-CAV in combination with the chemotherapeutic drugs, doxorubicin (DOX) or cisplatin (CIS), in cancer cells, especially in the absence of L-ARG. A combination method based on the median-effect principle and mass-action law was used. The following cancer cells were employed: HeLa and Caco-2 cells, overexpressing argininosuccinate synthase (ASS), pancreatic cells (MIA PaCa-2 and BxPC-3) and hepatocellular carcinoma cells (Hep G2 and SK-HEP-1), with down-regulated ASS. When constant and non-constant ratios of L-CAV were combined with DOX and CIS, a synergistic potentiation of cytotoxicity was recorded. Cells expressing high levels of ASS were more sensitive to the treatment as compared to the cells with reduced ASS levels. Overall, this study may provide a new approach to targeting some cancer cells with L-CAV in combination with DNA-targeting drugs such as DOX and CIS, especially those cells which overexpress ASS, such as human cervical and colorectal carcinoma cells. PeerJ Inc. 2016-01-07 /pmc/articles/PMC4734457/ /pubmed/26839743 http://dx.doi.org/10.7717/peerj.1542 Text en © 2016 Nurcahyanti and Wink http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Oncology
Nurcahyanti, Agustina DR
Wink, Michael
L-Canavanine potentiates the cytotoxicity of doxorubicin and cisplatin in arginine deprived human cancer cells
title L-Canavanine potentiates the cytotoxicity of doxorubicin and cisplatin in arginine deprived human cancer cells
title_full L-Canavanine potentiates the cytotoxicity of doxorubicin and cisplatin in arginine deprived human cancer cells
title_fullStr L-Canavanine potentiates the cytotoxicity of doxorubicin and cisplatin in arginine deprived human cancer cells
title_full_unstemmed L-Canavanine potentiates the cytotoxicity of doxorubicin and cisplatin in arginine deprived human cancer cells
title_short L-Canavanine potentiates the cytotoxicity of doxorubicin and cisplatin in arginine deprived human cancer cells
title_sort l-canavanine potentiates the cytotoxicity of doxorubicin and cisplatin in arginine deprived human cancer cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734457/
https://www.ncbi.nlm.nih.gov/pubmed/26839743
http://dx.doi.org/10.7717/peerj.1542
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