Martha E Cancino-Marentes1, Georgina Hernández-Flores2, Pablo Cesar Ortiz-Lazareno2, María Martha Villaseñor-García2, Eduardo Orozco-Alonso2, Erick Sierra-Díaz3, Raúl Antonio Solís-Martínez2, Claudia Carolina Cruz-Gálvez1, Alejandro Bravo-Cuellar4,5. 1. Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México. 2. División de Inmunología, Centro de Investigación Biomédica de Occidente del IMSS, Sierra Mojada 800, Col. Independencia, CP 44340, Guadalajara, Jalisco, México. 3. Servicio de Urología, Hospital de Especialidades, CMNO-IMSS, Guadalajara, Jalisco, México. 4. División de Inmunología, Centro de Investigación Biomédica de Occidente del IMSS, Sierra Mojada 800, Col. Independencia, CP 44340, Guadalajara, Jalisco, México. abravocster@gmail.com. 5. Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán de Morelos, Jalisco, México. abravocster@gmail.com.
Abstract
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.
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:PC3humanprostate 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 PC3humanprostate 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.
Authors: Esther M Speer; David J Dowling; Lukasz S Ozog; Jianjin Xu; Jie Yang; Geetika Kennady; Ofer Levy Journal: Pediatr Res Date: 2017-01-10 Impact factor: 3.756
Authors: José Manuel Lerma-Díaz; Georgina Hernández-Flores; Jorge R Domínguez-Rodríguez; Pablo C Ortíz-Lazareno; Piedad Gómez-Contreras; Ramón Cervantes-Munguía; Daniel Scott-Algara; Adriana Aguilar-Lemarroy; Luis F Jave-Suárez; Alejandro Bravo-Cuellar Journal: Immunol Lett Date: 2005-11-18 Impact factor: 3.685
Authors: O Gonzalez-Ramella; P C Ortiz-Lazareno; X Jiménez-López; S Gallegos-Castorena; G Hernández-Flores; F Medina-Barajas; J Meza-Arroyo; L F Jave-Suárez; J M Lerma-Díaz; F Sánchez-Zubieta; A Bravo-Cuellar Journal: Clin Transl Oncol Date: 2015-09-02 Impact factor: 3.405
Authors: R Solís-Martínez; M Cancino-Marentes; G Hernández-Flores; P Ortiz-Lazareno; G Mandujano-Álvarez; C Cruz-Gálvez; E Sierra-Díaz; C Rodríguez-Padilla; L F Jave-Suárez; A Aguilar-Lemarroy; A Bravo-Cuellar Journal: Immunol Lett Date: 2018-02-23 Impact factor: 3.685