4.7 Article

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

期刊

APOPTOSIS
卷 27, 期 1-2, 页码 49-69

出版社

SPRINGER
DOI: 10.1007/s10495-021-01699-5

关键词

Lung cancer; Coumarin; Benzophenone; JAK2/STAT3; Apoptosis

资金

  1. Lady Tata Memorial Trust
  2. VGST [VGST/P-2/CISEE/GRD-231/2013-14]
  3. SERB [EMR/2017/00088/]
  4. VGST, Bangalore, under CISEE Program [VGST/CISEE/282/2012-13]

向作者/读者索取更多资源

The study confirms BP-1C as a potential JAK2 specific inhibitor for lung cancer treatment, targeting apoptosis to inhibit tumor cell growth and progression.
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] .

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据