Anti-neoplastic phramacophore benzophenone-1 coumarin (BP-1C) targets JAK2 to induce apoptosis in lung cancer

Ankith, S. and Malojirao, Vikas H. and Thirusangu, Prabhu and Sharath, B. S. and Kandagalla, Shivananda and Vigneshwaran, V. and Novak, Jurica and Lakshmi, R. and Ramachandra, Y. L. and Baliga, Shrinath M. and Shaukath Ara Khanum and Prabhakar, B. T. (2021) Anti-neoplastic phramacophore benzophenone-1 coumarin (BP-1C) targets JAK2 to induce apoptosis in lung cancer. Apoptosis, 27. pp. 49-69.

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Abstract

Reigning of the abnormal gene activation associated with survival signalling in lung cancer leads to the anomalous growth and therapeutic failure. Targeting specific cell survival signalling like JAK2/STAT3 nexus has become a major focus of investigation to establish a target specific treatment. The 2-bromobenzoyl-4-methylphenoxy-acetyl hydra acetyl Coumarin (BP-1C), is new anti-neoplastic agent with apoptosis inducing capacity. The current study was aimed to develop antitumor phramacophore, BP-1C as JAK2 specific inhibitor against lung neoplastic progression. The study validates and identifies the molecular targets of BP-1C induced cell death. Cell based screening against multiple cancer cell lines identified, lung adenocarcinoma as its specific target through promotion of apoptosis. The BP-1C is able to induce, specific hall marks of apoptosis and there by conferring anti-neoplastic activity. Validation of its molecular mechanism, identified, BP-1C specifically targets JAK2(Tyr1007/1008) phosphorylation, and inhibits its downstream STAT3(Tyr705) signalling pathway to induce cell death. As a consequence, modulation in Akt/Src survival signal and altered expression of interwoven apoptotic genes were evident. The results were reproducible in an in-vivo LLC tumor model and in-ovo xenograft studies. The computational approaches viz, drug finger printing confers, BP-1C as novel class JAK2 inhibitor and molecular simulations studies assures its efficiency in binding with JAK2. Overall, BP-1C is a novel JAK2 inhibitor with experimental evidence and could be effectively developed into a promising drug for lung cancer treatment. GRAPHICS] .

Item Type:	Article
Uncontrolled Keywords:	Lung cancer; Coumarin; Benzophenone; JAK2/STAT3; Apoptosis
Subjects:	C Chemical Science > Chemistry
Divisions:	Yuvaraj college > Chemistry
Depositing User:	Mr Umendra uom
Date Deposited:	05 Mar 2022 05:11
Last Modified:	05 Jul 2022 07:32
URI:	http://eprints.uni-mysore.ac.in/id/eprint/17275

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