Cytotoxic Effect of Acetone-Treated Docetaxel on PC3 and PNT1A Cells

Year 2021, Volume: 10 Issue: 2, 109 - 120, 30.12.2021

Muhammed Güngören , Ersin Kılınç , Zübeyde Baysal

Abstract

In this study, the cytotoxic effects of docetaxel, which is used as an important chemotherapeutic agent in the treatment of prostate cancer, on human intact prostate cell (PNT1A) and human cancerous prostate cell (PC3) were investigated. In the study, pure and acetone-soaked form of commercial docetaxel was used. It was determined that there was no significant difference between the use of different forms of docetaxel in the analyzes performed after 24, 48 and 72 hours of incubation using the MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] test (p<0.01). It was found that docetaxel forms have dose dependent cytotoxic effects on PC3 and PNT1A cells. It was determined that the dose dependence of the cytotoxic effect was quite high, especially in the first 24 hours (p<0.05 for PC3, p<0.01 for PNT1A). The IC50 value of pure docetaxel for PC3 cell was calculated as 0.0116 μg/mL and for PNT1A cell as 3.5462 μg/mL at 48. h. These values show that docetaxel produces a cytotoxic effect in PNT1A cells, although it is lower than in PC3 cells. Using docetaxel, which has therapeutic effects in resistant prostate cancer cells, together with drug delivery systems is considered as an appropriate approach for reducing the damage in healthy cells.

Keywords

Docetaxel , MIT assay , Prostate cancer , Cytotoxicity-dose correlation

Project Number

Proje Numarası: TEKNİK-MYO-19-001 ve FEN.19.015

Asetonla Muamele Edilmiş Docetaxelin PC3 ve PNT1A Hücreleri Üzerindeki Sitotoksik Etkisi

Abstract

Bu çalışmada, prostat kanserinin tedavisinde önemli bir kemoterapötik ajan olarak kullanılan docetaxelin, insan sağlam prostat hücresi (PNT1A) ve insan kanserli prostat hücresi (PC3) üzerindeki sitotoksik etkileri araştırılmıştır. Çalışmada ticari docetaxelin saf ve asetonda bekletilmiş formu kullanılmıştır. MTT [3-(4,5-dimetiltiazol-2-il)-2,5-difenil-2H-tetrazolyum bromid] testi kullanılarak 24, 48 ve 72 saatlik inkübasyon sonrası yapılan analizlerde farklı docetaxel formlarının kullanımı arasında anlamlı bir fark bulunmadığı tespit edilmiştir (p<0.01). Elde edilen bulgular, docetaxel formlarının PC3 ve PNT1A hücreleri üzerinde doza bağımlı sitotoksik etkilerinin varlığını ortaya koymaktadır. Sitotoksik etkinin doza bağımlılığının özellikle ilk 24 saatte oldukça yüksek olduğu belirlenmiştir (PC3 için p<0.05, PNT1A için p<0.01). 48. saatte saf docetaxelin PC3 hücresi için IC50 değeri 0.0116 μg/mL, PNT1A hücresi için IC50 değeri 3.5462 μg/mL olarak hesaplanmıştır. Bu değerler docetaxelin PNT1A hücrelerinde, PC3 hücrelerine kıyasla daha düşük olsada, sitotoksik etki oluşturduğunu göstermektedir. Direnç geliştirmiş prostat kanseri hücrelerinde de terapötik etkileri olan docetaxelin ilaç taşıma sistemleri ile beraber kullanılarak sağlam hücrelerdeki hasarının azaltılması uygun bir yaklaşım olarak düşünülmektedir.

Keywords

Docetaxel , MTT testi , Prostat kanseri , Sitotoksisite-doz ilişkisi

Supporting Institution

Dicle Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi Koordinatörlüğü

Project Number

Proje Numarası: TEKNİK-MYO-19-001 ve FEN.19.015

Thanks

Bu araştırma, Dicle Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi Koordinatörlüğü’nce desteklenmiştir (Proje Numarası: TEKNİK-MYO-19-001 ve FEN.19.015).

References

• D. Hanahan and R. A. Weinberg, “Hallmarks of cancer: The next generation,” Cell, vol. 144, pp. 646-674, 2011.
• R. K. Dubey, A. P. Singh and N. Dwivedi, “Triorganotin (IV) derivatives of bidentate schiff bases: Synthesis and spectral studies,” Phosphorus Sulfur., vol. 187, no. 9, pp. 1038-1045, 2012.
• P. Kesharwani, L. Xie, S. Banerjee, G. Mao, S. Padhye, F. H. Sarkar and A. K. Iyer, “Hyaluronic acid-conjugated polyamidoamine dendrimers for targeted delivery of 3,4-difluorobenzylidene curcumin to CD44 overexpressing pancreatic cancer cells,” Colloid. Surface. B, vol. 136, pp. 413-423, 2015.
• A. K. Sharma, A. Gothwal, P. Kesharwani, H. Alsaab, A. K. Iyer and U. Gupta, “Dendrimer nanoarchitectures for cancer diagnosis and anticancer drug delivery,” Drug Discov. Today, vol. 22, no. 2, pp. 314-326, 2017.
• Globocan, (2020). Cancer Fact Sheets. Erişim Tarihi: 10.05.2021. [Online]. https://gco.iarc.fr/today/fact-sheets-cancers.
• U. Testa, G. Castelli and E. Pelosi, “Cellular and molecular mechanisms underlying prostate cancer development: Therapeutic implications,” Medicines, vol. 6, no.3, pp. 82, 2019, doi: 10.3390/medicines6030082.
• S. M. Elmi, “Investigation of Catechol-o-methyl transferase (Comt) gene Val158met polymorphism and its relationship with prostate cancer,” M.S. thesis, Dept. Mol. Med., Yeditepe Univ., Istanbul, Turkey, 2020.
• L. Brannon-Peppas and J. O. Blanchette, “Nanoparticle and targeted systems for cancer therapy,” Adv. Drug Deliver. Rev., vol. 64, pp. 206-212, 2012.
• S. Jain, P. Kesharwani, R. K. Tekade and N. K. Jain, “One platform comparison of solubilization potential of dendrimer with some solubilizing agents,” Drug Dev. Ind. Pharm., vol. 41, no. 5, pp. 722-727, 2015.
• J. J. Hendrikx, J. S. Lagas, J. Y. Song, H. Rosing, J. H. M. Schellens, J. H. Beijnen, S. Rottenberg and A. H. Schinkel, “Ritonavir inhibits intratumoral docetaxel metabolism and enhances docetaxel antitumor activity in an immunocompetent mouse breast cancer model,” Int. J. Cancer, vol.138, no. 3, pp 758-769, 2016.
• E. T. Oh, C.W. Kim, S. J. Kim, J. S. Lee, S. S. Hong and H.J. Park, “Docetaxel induced-JNK2/PHD1 signaling pathway increases degradation of HIF-1α and causes cancer cell death under hypoxia,” Sci. Rep-UK., vol. 6, 2016, Art no. 27382.
• D. I. Quinn, H.M. Sandler, L.G. Horvath, A. Goldkorn and J.A. Eastham, “The evolution of chemotherapy for the treatment of prostate cancer,” Ann. Oncol., vol. 28, no. 11, pp. 2658–2669, 2017.
• S. Sumanasuriya and J. De Bono, “Treatment of advanced prostate cancer-a review of current therapies and future promise,” Cold Spring Harb. Persp. Med., vol. 8, no. 6, 2018, Art no. 030635, doi: 10.1101/cshperspect.a030635.
• L. Li, F. Tang, H. Liu, T. Liu, N. Hao, D. Chen, X. Teng, J. He, “In vivo delivery of silica nanorattle encapsulated docetaxel for liver cancer therapy with low toxicity and high efficacy,” ACS Nano, vol. 4, pp. 6874–6882, 2010, doi: http://dx.doi.org/10.1021/nn100918a.
• R. S. Herbst and F. R. Khuri, “Mode of action of docetaxel—a basis for combination with novel anticancer agents,” Cancer Treat. Rev., vol. 29, pp. 407–415, 2003.
• Y. Liu, K. Li, J. Pan, B. Liu and S. S. Feng, “Folic acid conjugated nanoparticles of mixed lipid monolayer shell and biodegradable polymer core for targeted delivery of Docetaxel,” Biomaterials, vol. 31, pp. 330–338, 2010.
• S. Zhao, S. Tan, Y. Guo, J. Huang, M. Chu, H. Liu and Z. Zhang, “pH-sensitive docetaxel-loaded D-a-tocopheryl polyethylene glycol succinate-poly(b-amino ester) copolymer nanoparticles for overcoming multidrug resistance,” Biomacromolecules, vol. 14, pp. 2636–2646, 2013.
• H. Zhu, H. Chen, X. Zeng, Z. Wang, X. Zhang, Y. Wu, Y. Gao, J. Zhang, K. Liu, R. Liu, L. Cai, L. Mei and S. S.Feng, “Co-delivery of chemotherapeutic drugs with vitamin E TPGS by porous PLGA nanoparticles for enhanced chemotherapy against multi-drug resistance,” Biomaterials, vol. 35, pp. 2391–2400, 2014.
• P. K. B. Nagesh, N. R. Johnson, V. K.N. Boya, P. Chowdhury, S. F. Othman, V. Khalilzad-Sharghi, B. B. Hafeez, A. Ganju, S. Khan, S. W. Behrman, N. Zafar, S. C. Chauhan, M. Jaggi and M. M. Yallapu, “PSMA targeted docetaxel-loaded superparamagnetic iron oxide nanoparticles for prostate cancer,” Colloid. Surface. B, vol. 144, pp. 8-20, 2016.
• Electron Microscopy Sciences. (2021). Erişim tarihi: 15.05.2021. [Online]. https://www.emsdiasum.com/microscopy/technical/datasheet/68052-14.aspx.
• T. Mosmann, “Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays,” J. Immunol. Methods, vol. 65, no. 1–2, pp. 55–63, 1983.
• L. N. F. Trevizan, J. O. Eloy, M. T. Luiz, R. Petrilli, S. L. Ramos Junior, J. C. Borges, J. M. Marchetti and M. Chorilli, “Anti-EGFR liquid crystalline nanodispersions for docetaxel delivery: Formulation, characterization and cytotoxicity in cancer cells,” Colloid. Surface. A, vol 613, 2021, Art no. 126058.
• M. Monteverde, F. Tonissi, J. L. Fischel, M. C. Etienne-Grimaldi, G. Milano, M. Merlano and C. Lo Nigro, “Combination of docetaxel and vandetanib in docetaxel-sensitive or resistant PC3 cell line,” Urol. Oncol., vol. 31, no. 6, pp. 776-786, 2013.
• M. A. Fernandes, J. O. Eloy, M. T. Luiz, S. L. Ramos Junior, J. C. Borges, L. R. de la Fuente, C. O. de San Luis, J. M. Marchetti, M. J. Santos-Martinez ve M. Chorilli, “Transferrin-functionalized liposomes for docetaxel delivery to prostate cancer cells,” Colloid. Surface. A, vol. 611, 2021, Art no. 125806.
• Y. Morikawa, H. Koike, Y. Sekine, H. Matsui, Y. Shibata, K. Ito, K. Suzuki, “Rapamycin enhances docetaxel-induced cytotoxicity in an androgen-independent prostate cancer xenograft model by surviving downregulation,” Biochem. Biophys. Res. Commun., vol. 419, no. 3, pp. 584-589, 2012.
• H. Sasaki, L. H. Klotz, L. M. Sugar, A. Kiss and V. Venkateswaran, “A combination of desmopressin and docetaxel inhibit cell proliferation and invasion mediated by urokinase-type plasminogen activator (uPA) in human prostate cancer cells,” Biochem. Biophys. Res. Commun., vol. 464, no. 3, pp. 848-854, 2015.