Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ilam University of Medical Sciences

Sildenafil enhances cisplatin-induced apoptosis in human breast adenocarcinoma cells

Thu Oct 6 07:20:55 2022

(2020) Sildenafil enhances cisplatin-induced apoptosis in human breast adenocarcinoma cells. Journal of Cancer Research and Therapeutics. pp. 1412-1418. ISSN 0973-1482

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Abstract

Introduction: Cyclic nucleotide phosphodiesterase (PDE) enzymes are a large superfamily of enzymes that catalyze the conversion reaction of cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP) to AMP and GMP, respectively. In some cancer cells, PDE-5 has been shown to be overexpressed in multiple human carcinomas. It seems that the inhibition of PDE-5 may has anticancer effects. Cisplatin is one of the prevalent chemo-agents to treat solid tumors. However, its clinical usefulness is hindered by dose-limiting toxicities, especially on the kidneys (nephrotoxicity) and ears (ototoxicity). In this study, the antitumor activity of the sildenafil as a PDE-5 inhibitor alone and in combination with cisplatin on human mammary adenocarcinomas and MCF-7 and MDA-MB-468 was assessed. Materials and Methods: Sildenafil as PDE type 5 (PDE5) inhibitor is the drugs that we combined with the cisplatin (chemotherapeutic agent), in vitro. Human mammary adenocarcinomas and MCF-7 and MDA-MB-468 cell lines were cultured in standard conditions. At time point, following 24 h and 48 h incubation, the cell lines were treated by cisplatin in the presence/absence of sildenafil. Cell viability, apoptosis, and reactive oxygen species (ROS) were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, real-time polymerase chain reaction, and Western blot; and fluorimetric methods, respectively. Statistical analysis was performed using SPSS software SPSS (SPSS Inc., Chicago, IL, USA). Results: In MCF-7 cell line, following 24 h incubation, combinations of sildenafil with cisplatin (P < 0.001) showed decreased cell viability when compared to sildenafil and cisplatin alone. Moreover in MDA-MB-468 cell line, following 24 h incubation, data did not show any significant changes on cell viability when treated with cisplatin, in the presence or absence of sildenafil. However, following 48 h incubation, combinations of cisplatin with sildenafil (P < 0.001) were showed decreased cell viability when compared to cisplatin and sildenafil alone in both MCF-7 and MDA-MB-468 cell lines. Concerning the ROS production and apoptosis, data showed that both processes increase significantly in the presence of the sildenafil in comparison absent it. Conclusion: Our data showed that the combination of sildenafil with cisplatin can improve cell toxicity and anticancer effect of cisplatin. And also sildenafil as a PDE-5 inhibitor could be used as additive treatment in combination with cisplatin to make a reduction in cisplatin dosage and its side effects.

Item Type: Article
Creators:
CreatorsEmail
Hassanvand, F.UNSPECIFIED
Mohammadi, T.UNSPECIFIED
Ayoubzadeh, N.UNSPECIFIED
Tavakoli, A.UNSPECIFIED
Hassanzadeh, N.UNSPECIFIED
Sanikhani, N.UNSPECIFIED
Azimi, A. I.UNSPECIFIED
Mirzaei, H. R.UNSPECIFIED
Khodamoradi, M.UNSPECIFIED
Goudarzi, K. A.UNSPECIFIED
Pourghadamyari, H.UNSPECIFIED
Zaimy, M. A.UNSPECIFIED
Keywords: Antitumor activity apoptosis breast cancer cisplatin sildenafil molecular-mechanisms pde5 inhibitors anticancer activity cancer combination therapy resistance ros Oncology
Divisions:
Page Range: pp. 1412-1418
Journal or Publication Title: Journal of Cancer Research and Therapeutics
Journal Index: ISI
Volume: 16
Number: 6
Identification Number: https://doi.org/10.4103/jcrt.JCRT₆₇₅₁₉
ISSN: 0973-1482
Depositing User: مهندس مهدی شریفی
URI: http://eprints.medilam.ac.ir/id/eprint/3358

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