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

Autor: Cancino-Marentes ME; Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México., Hernández-Flores G; División de Inmunología, Centro de Investigación Biomédica de Occidente del IMSS, Sierra Mojada 800, Col. Independencia, CP 44340, Guadalajara, Jalisco, México., Ortiz-Lazareno PC; División de Inmunología, Centro de Investigación Biomédica de Occidente del IMSS, Sierra Mojada 800, Col. Independencia, CP 44340, Guadalajara, Jalisco, México., Villaseñor-García MM; División de Inmunología, Centro de Investigación Biomédica de Occidente del IMSS, Sierra Mojada 800, Col. Independencia, CP 44340, Guadalajara, Jalisco, México., Orozco-Alonso E; División de Inmunología, Centro de Investigación Biomédica de Occidente del IMSS, Sierra Mojada 800, Col. Independencia, CP 44340, Guadalajara, Jalisco, México., Sierra-Díaz E; Servicio de Urología, Hospital de Especialidades, CMNO-IMSS, Guadalajara, Jalisco, México., Solís-Martínez RA; División de Inmunología, Centro de Investigación Biomédica de Occidente del IMSS, Sierra Mojada 800, Col. Independencia, CP 44340, Guadalajara, Jalisco, México., Cruz-Gálvez CC; Doctorado en Farmacología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México., Bravo-Cuellar A; División de Inmunología, Centro de Investigación Biomédica de Occidente del IMSS, Sierra Mojada 800, Col. Independencia, CP 44340, Guadalajara, Jalisco, México. abravocster@gmail.com.; Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán de Morelos, Jalisco, México. abravocster@gmail.com.
Jazyk: angličtina
Zdroj: BMC urology [BMC Urol] 2021 Mar 12; Vol. 21 (1), pp. 38. Date of Electronic Publication: 2021 Mar 12.
DOI: 10.1186/s12894-021-00807-6
Abstrakt: 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.
Databáze: MEDLINE
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