Identification of a Novel 1,2 Oxazine That Can Induce Apoptosis by Targeting NF-κB in Hepatocellular Carcinoma Cells

Publication date: Available online 19 February 2020Source: Biotechnology ReportsAuthor(s): Chaithanya Somu, Chakrabhavi Dhananjaya Mohan, Sachin Ambedkar, Dukanya, Shobith Rangappa, CP Baburajeev, Alexey Sukhorukov, Srishti Mishra, Muthu K Shanmugam, Arunachalam Chinnathambi, Tahani Awad Alahmadi, Sulaiman Ali Alharbi, Basappa, Kanchugarakoppal S. RangappaAbstractConstitutive activation of NF-κB is associated with proinflammatory diseases and suppression of the NF-κB signaling pathway has been considered as an effective therapeutic strategy in the treatment of various cancers including hepatocellular carcinoma (HCC). Herein, we report the synthesis of 1,2 oxazines and their anticancer potential. The antiproliferative studies presented 3-((4-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)methyl)-4-phenyl-4,4a,5,6,7,7a-hexahydrocyclopenta [e][1,2]oxazine(3i) as a lead cytotoxic agent against HCC cells. Flow cytometric analysis showed that 3i caused a substantial increase in the subG1 cell population. Annexin-V-FITC-PI staining showed a significant increase in the percentage of apoptotic cells on treatment with 3i. Transfection with p65 siRNA significantly reduced the 3i induced DNA fragmentation indicating that 3i may primarily mediate its proapoptotic effects by abrogating the NF-κB signaling. In addition, treatment of HCC cells with 3i decreased the DNA binding ability of NF-κB and NF-κB-dependent luciferase expression. Taken together, this report introduces 1,2-oxazine that p...
Source: Biotechnology Reports - Category: Biotechnology Source Type: research