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
Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
Urology,Reproductive Medicine,General Medicine
Reference37 articles.
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34.
3. Testa U, Castelli G, Pelosi E. Cellular and molecular mechanisms underlying prostate cancer development: therapeutic implications. Medicines (Basel). 2019;6(3):1–139.
4. Gleason DF. Histologic grading of prostate cancer: a perspective. Hum Pathol. 1992;23(3):273–9.
5. Johansson JE, Adami HO, Andersson SO, Bergström R, Holmberg L, Krusemo UB. High 10-year survival rate in patients with early, untreated prostatic cancer. JAMA. 1992;267(16):2191–6.
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献