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Combination drug therapy for multimodal treatment of cancer by targeting mitochondrial transcriptional pathway: An in-silico approach. | LitMetric

Combination drug therapy for multimodal treatment of cancer by targeting mitochondrial transcriptional pathway: An in-silico approach.

Med Hypotheses

Department of Biotechnology Engineering, Institute of Engineering and Technology, Bundelkhand University, Jhansi 284128, India; Department of Biochemical Engineering and Biotechnology. Indian Institute of Technology, Hauz Khas, New Delhi 110016, India.

Published: October 2020

AI Article Synopsis

Article Abstract

Cancer pathologies are deeply associated with mitochondrial dysfunction. TFAM, transcription factor A of mitochondria plays eminent role in transcription and replication of mtDNA to synthesize different mitochondrial proteins, has been reported to have elevated levels during malignancy and can be a compelling target of the disease. We hypothesize that violacein and silver nanoparticles, as a dyad drug system, can structurally bind and inhibit TFAM at the interface of TFAM-DNA complex during replication and thus can hinder majority of pathways contributing to cancer proliferation. It is evident from our molecular docking analysis of violacein and silver nanoparticles with the TFAM-DNA complex which gave resulting negative binding energy of -8.836 kcal/mol for violacein with inhibition constant (Ki value) of 1.51 μM and high binding score of 9518 for silver nanoparticle in the DNA interacting cavity of TFAM. Hence, our hypothesis of employing violacein and silver nanoparticle for cancer treatment by TFAM inhibition seems highly promising and further in-vitro and in-vivo studies are extremely demanded in this concern.

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Source
http://dx.doi.org/10.1016/j.mehy.2020.110075DOI Listing

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