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Sensitizing the cytotoxic action of Docetaxel induced by Pentoxifylline in a PC3 prostate cancer cell line

BACKGROUND: Prostate cancer is one of the most frequently diagnosed types of cancers worldwide. In its initial period, the tumor is hormone-sensitive, but in advanced states, it evolves into a metastatic castration-resistant tumor. In this state, chemotherapy with taxanes such as Docetaxel (DTX) com...

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Autores principales: Cancino-Marentes, Martha E., Hernández-Flores, Georgina, Ortiz-Lazareno, Pablo Cesar, Villaseñor-García, María Martha, Orozco-Alonso, Eduardo, Sierra-Díaz, Erick, Solís-Martínez, Raúl Antonio, Cruz-Gálvez, Claudia Carolina, Bravo-Cuellar, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953714/
https://www.ncbi.nlm.nih.gov/pubmed/33711972
http://dx.doi.org/10.1186/s12894-021-00807-6
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author Cancino-Marentes, Martha E.
Hernández-Flores, Georgina
Ortiz-Lazareno, Pablo Cesar
Villaseñor-García, María Martha
Orozco-Alonso, Eduardo
Sierra-Díaz, Erick
Solís-Martínez, Raúl Antonio
Cruz-Gálvez, Claudia Carolina
Bravo-Cuellar, Alejandro
author_facet Cancino-Marentes, Martha E.
Hernández-Flores, Georgina
Ortiz-Lazareno, Pablo Cesar
Villaseñor-García, María Martha
Orozco-Alonso, Eduardo
Sierra-Díaz, Erick
Solís-Martínez, Raúl Antonio
Cruz-Gálvez, Claudia Carolina
Bravo-Cuellar, Alejandro
author_sort Cancino-Marentes, Martha E.
collection PubMed
description BACKGROUND: Prostate cancer is one of the most frequently diagnosed types of cancers worldwide. In its initial period, the tumor is hormone-sensitive, but in advanced states, it evolves into a metastatic castration-resistant tumor. In this state, chemotherapy with taxanes such as Docetaxel (DTX) comprises the first line of treatment. However, the response is poor due to chemoresistance and toxicity. On the other hand, Pentoxifylline (PTX) is an unspecific inhibitor of phosphodiesterases; experimental, and clinically it has been described as sensitizing tumor cells to chemotherapy, increasing apoptosis and decreasing senescence. We study whether the PTX sensitizes prostate cancer cells to DTX for greater effectiveness. METHODS: PC3 human prostate cancer cells were treated in vitro at different doses and times with PTX, DTX, or their combination. Viability was determined by the WST-1 assay by spectrophotometry, cell cycle progression, apoptosis, generic caspase activation and senescence by flow cytometry, DNA fragmentation and caspases-3, -8, and -9 activity by ELISA. RESULTS: We found that PTX in PC3 human prostate cancer cells induces significant apoptosis per se and increases that generated by DTX, while at the same time it reduces the senescence caused by the chemotherapy and increases caspases-3,-8, and -9 activity in PTX + DTX-treated cells. Both treatments blocked the PC3 cell in the G1 phase. CONCLUSIONS: Our results show that PTX sensitizes prostate tumor cells to apoptosis induced by DTX. Taken together, the results support the concept of chemotherapy with rational molecular bases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12894-021-00807-6.
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spelling pubmed-79537142021-03-12 Sensitizing the cytotoxic action of Docetaxel induced by Pentoxifylline in a PC3 prostate cancer cell line Cancino-Marentes, Martha E. Hernández-Flores, Georgina Ortiz-Lazareno, Pablo Cesar Villaseñor-García, María Martha Orozco-Alonso, Eduardo Sierra-Díaz, Erick Solís-Martínez, Raúl Antonio Cruz-Gálvez, Claudia Carolina Bravo-Cuellar, Alejandro BMC Urol Research Article BACKGROUND: Prostate cancer is one of the most frequently diagnosed types of cancers worldwide. In its initial period, the tumor is hormone-sensitive, but in advanced states, it evolves into a metastatic castration-resistant tumor. In this state, chemotherapy with taxanes such as Docetaxel (DTX) comprises the first line of treatment. However, the response is poor due to chemoresistance and toxicity. On the other hand, Pentoxifylline (PTX) is an unspecific inhibitor of phosphodiesterases; experimental, and clinically it has been described as sensitizing tumor cells to chemotherapy, increasing apoptosis and decreasing senescence. We study whether the PTX sensitizes prostate cancer cells to DTX for greater effectiveness. METHODS: PC3 human prostate cancer cells were treated in vitro at different doses and times with PTX, DTX, or their combination. Viability was determined by the WST-1 assay by spectrophotometry, cell cycle progression, apoptosis, generic caspase activation and senescence by flow cytometry, DNA fragmentation and caspases-3, -8, and -9 activity by ELISA. RESULTS: We found that PTX in PC3 human prostate cancer cells induces significant apoptosis per se and increases that generated by DTX, while at the same time it reduces the senescence caused by the chemotherapy and increases caspases-3,-8, and -9 activity in PTX + DTX-treated cells. Both treatments blocked the PC3 cell in the G1 phase. CONCLUSIONS: Our results show that PTX sensitizes prostate tumor cells to apoptosis induced by DTX. Taken together, the results support the concept of chemotherapy with rational molecular bases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12894-021-00807-6. BioMed Central 2021-03-12 /pmc/articles/PMC7953714/ /pubmed/33711972 http://dx.doi.org/10.1186/s12894-021-00807-6 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Cancino-Marentes, Martha E.
Hernández-Flores, Georgina
Ortiz-Lazareno, Pablo Cesar
Villaseñor-García, María Martha
Orozco-Alonso, Eduardo
Sierra-Díaz, Erick
Solís-Martínez, Raúl Antonio
Cruz-Gálvez, Claudia Carolina
Bravo-Cuellar, Alejandro
Sensitizing the cytotoxic action of Docetaxel induced by Pentoxifylline in a PC3 prostate cancer cell line
title Sensitizing the cytotoxic action of Docetaxel induced by Pentoxifylline in a PC3 prostate cancer cell line
title_full Sensitizing the cytotoxic action of Docetaxel induced by Pentoxifylline in a PC3 prostate cancer cell line
title_fullStr Sensitizing the cytotoxic action of Docetaxel induced by Pentoxifylline in a PC3 prostate cancer cell line
title_full_unstemmed Sensitizing the cytotoxic action of Docetaxel induced by Pentoxifylline in a PC3 prostate cancer cell line
title_short Sensitizing the cytotoxic action of Docetaxel induced by Pentoxifylline in a PC3 prostate cancer cell line
title_sort sensitizing the cytotoxic action of docetaxel induced by pentoxifylline in a pc3 prostate cancer cell line
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953714/
https://www.ncbi.nlm.nih.gov/pubmed/33711972
http://dx.doi.org/10.1186/s12894-021-00807-6
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