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Anti-neoplastic pharmacophore benzophenone-1 coumarin (BP-1C) targets JAK2 to induce apoptosis in lung cancer.
- Source :
-
Apoptosis : an international journal on programmed cell death [Apoptosis] 2022 Feb; Vol. 27 (1-2), pp. 49-69. Date of Electronic Publication: 2021 Nov 27. - Publication Year :
- 2022
-
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 <superscript>Tyr1007/1008</superscript> phosphorylation, and inhibits its downstream STAT3 <superscript>Tyr705</superscript> 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.<br /> (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Details
- Language :
- English
- ISSN :
- 1573-675X
- Volume :
- 27
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Apoptosis : an international journal on programmed cell death
- Publication Type :
- Academic Journal
- Accession number :
- 34837562
- Full Text :
- https://doi.org/10.1007/s10495-021-01699-5