Digoxin Inhibits Retinoblastoma through Suppressing a Non-canonical TGFβ Signaling Pathway.

Sheikhzade, Maryam. and Akbari, Abolfazl. and Karkhaneh, Reza. and Ghassemi, Fariba. and Sadeghi, Abdolrahim. and Shahrzad Kavakani, Mahshid. and Mobini, Gholam Reza. and Mohebbi, Masoumeh. and Heidari, Mansour. (2016) Digoxin Inhibits Retinoblastoma through Suppressing a Non-canonical TGFβ Signaling Pathway. British Journal of Medicine & Medical Research, 15 (6).

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Abstract

Aims: Retinoblastoma is a childhood ocular tumor rapidly developing from the immature cells of the retina due to loss of functional retinoblastoma protein. Digoxin, a cardiac glycoside, has been reported to be effective in inducing apoptosis, cell cycle arrest, and cytotoxic effects on human cancers. In this regard, the present study aims to investigate whether digoxin could suppress retinoblastoma cancer through the regulation of transforming growth factor-β (TGF-β) signaling pathway. Methodology: The effects of digoxin on Y-79 cells, retinoblastoma cancer cell line, were investigated using MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazoli-umbromide) and BrdU (bromodeoxyuridine) assays to measure cellular cytotoxicity effects and cell apoptosis, respectively. Also, a qPCR assay was employed to analyze the mRNA expression levels of TGFβ signaling pathway including C-MYC, P21, P15, TGFβRI, TGFβRII, and SMAD2, 3, and 4 genes. Results: The results of the cell function assays revealed that digoxin inhibited the cell viability and proliferation of Y-79 cells. In addition, it was found that digoxin significantly suppressed C-MYC expression and enhanced the expression of P21, P15, SMAD2 and SMAD4 genes in a dose-and time-dependent manner. However, the obtained results could not detect any significant effect of digoxin on TGFβRI, TGFβRII and SMAD3 genes. Conclusion: Taken together, the findings of the present study suggest that digoxin could be a potential therapeutic agent in the treatment of retinoblastoma by regulating the cell cycle genes via a non-canonical TGF-β signaling pathway.

Item Type: Article
Uncontrolled Keywords: c-Myc; eye cancer; gene expression; P21; P15; real-time PCR.
Subjects: QU Biochemistry
QZ pathology-Neoplasms
Divisions: Reserach Vice-Chancellar Department > Medical Plants Research Center
Depositing User: zahra bagheri .
Date Deposited: 21 Nov 2017 06:26
Last Modified: 13 Feb 2018 11:17
URI: http://eprints.skums.ac.ir/id/eprint/6380

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