Repurposing mechanistic insight of PDE-5 inhibitor in cancer chemoprevention through mitochondrial-oxidative stress intervention and blockade of DuCLOX signalling

通过线粒体氧化应激干预和阻断 DuCLOX 信号,重新利用 PDE-5 抑制剂在癌症化学预防中的机制见解

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作者:Manjari Singh #, Sweta Kasna #, Subhadeep Roy, Sara Aldosary, Abdulaziz S Saeedan, Mohd Nazam Ansari, Gaurav Kaithwas

Background

This study evaluates the anti-cancer effects of Tadalafil (potent PDE-5 inhibitor) in female albino wistar rats against n-methyl n-nitrosourea induced mammary gland carcinogenesis.

Conclusion

The results confirm that Tadalafil treatment restored all the biological markers to the normal and its involvement in mitochondrial mediated death apoptosis pathway along with inhibition of inflammatory markers.

Methods

The animals were selected and randomly divided among four groups and each group contains six animals per group. The animal tissue and serum samples were evaluated for the presence of antioxidant parameters and the cellular morphology was studied using carminic staining, haematoxylin staining and scanning electron microscopy followed by immunoblotting analysis.

Results

On the grounds of hemodynamic recordings and morphology, n-methyl n-nitrosourea treated group showed distorted changes along with distorted morphological parameters. For morphological analysis, the mammary gland tissues were evaluated using scanning electron microscopy, whole mount carmine staining, haematoxylin and eosin staining. The serum samples were evaluated for the evaluation of oxidative stress markers and inflammatory markers. The level of caspase 3 and 8 were also evaluated for the estimation of apoptosis. The fatty acid profiling of mammary gland tissue was evaluated using fatty acid methyl esters formation. The mitochondrial mediated apoptosis and inflammatory markers were evaluated using immunoblotting assay.

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