Identification of a novel 1,2 oxazine that can induce apoptosis by targeting NF-κB in hepatocellular carcinoma cells
Constitutive 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 ox...
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Elsevier
2020-03-01
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| Series: | Biotechnology Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2215017X19307295 |
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doaj-8e5f088fb9c84db59bc215b3ee91a0f42020-11-25T02:40:35ZengElsevierBiotechnology Reports2215-017X2020-03-0125Identification of a novel 1,2 oxazine that can induce apoptosis by targeting NF-κB in hepatocellular carcinoma cellsChaithanya Somu0Chakrabhavi Dhananjaya Mohan1Sachin Ambekar2 Dukanya3Shobith Rangappa4CP Baburajeev5Alexey Sukhorukov6Srishti Mishra7Muthu K Shanmugam8Arunachalam Chinnathambi9Tahani Awad Alahmadi10Sulaiman Ali Alharbi11 Basappa12Kanchugarakoppal S. Rangappa13Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570006, IndiaDepartment of Studies in Molecular Biology, University of Mysore, Manasagangotri, Mysore 570006, IndiaLaboratory of Chemical Biology, Department of Chemistry, Bangalore University, Central College Campus, Palace Road, Bangalore 560001, IndiaLaboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore 570006, IndiaAdichunchanagiri Institute for Molecular Medicine, BG Nagara, Nagamangala Taluk, Mandya district-571448, IndiaLaboratory of Chemical Biology, Department of Chemistry, Bangalore University, Central College Campus, Palace Road, Bangalore 560001, IndiaN.D. Zelinsky Institute of Organic Chemistry, Leninsky Prospect, Moscow 119991, RussiaDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore 117600, SingaporeDepartment of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore 117600, SingaporeDepartment of Botany and Microbiology, College of Science, King Saud University, Riyadh -11451, Saudi ArabiaDepartment of Pediatrics, College of Medicine and King Khalid University Hospital, King Saud University Medical City, Riyadh 11461, Saudi ArabiaDepartment of Botany and Microbiology, College of Science, King Saud University, Riyadh -11451, Saudi ArabiaLaboratory of Chemical Biology, Department of Chemistry, Bangalore University, Central College Campus, Palace Road, Bangalore 560001, India; Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India; Corresponding author at: Laboratory of Chemical Biology, Department of Chemistry, Bangalore University, Central College Campus, Palace Road, Bangalore 560001, India.Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India; Corresponding author.Constitutive 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 potently targets the NF-κB signaling pathway in HCC cells. Keywords: Oxazine, NF-κB, Anticancer, DNA fragmentationhttp://www.sciencedirect.com/science/article/pii/S2215017X19307295 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Chaithanya Somu Chakrabhavi Dhananjaya Mohan Sachin Ambekar Dukanya Shobith Rangappa CP Baburajeev Alexey Sukhorukov Srishti Mishra Muthu K Shanmugam Arunachalam Chinnathambi Tahani Awad Alahmadi Sulaiman Ali Alharbi Basappa Kanchugarakoppal S. Rangappa |
| spellingShingle |
Chaithanya Somu Chakrabhavi Dhananjaya Mohan Sachin Ambekar Dukanya Shobith Rangappa CP Baburajeev Alexey Sukhorukov Srishti Mishra Muthu K Shanmugam Arunachalam Chinnathambi Tahani Awad Alahmadi Sulaiman Ali Alharbi Basappa Kanchugarakoppal S. Rangappa Identification of a novel 1,2 oxazine that can induce apoptosis by targeting NF-κB in hepatocellular carcinoma cells Biotechnology Reports |
| author_facet |
Chaithanya Somu Chakrabhavi Dhananjaya Mohan Sachin Ambekar Dukanya Shobith Rangappa CP Baburajeev Alexey Sukhorukov Srishti Mishra Muthu K Shanmugam Arunachalam Chinnathambi Tahani Awad Alahmadi Sulaiman Ali Alharbi Basappa Kanchugarakoppal S. Rangappa |
| author_sort |
Chaithanya Somu |
| title |
Identification of a novel 1,2 oxazine that can induce apoptosis by targeting NF-κB in hepatocellular carcinoma cells |
| title_short |
Identification of a novel 1,2 oxazine that can induce apoptosis by targeting NF-κB in hepatocellular carcinoma cells |
| title_full |
Identification of a novel 1,2 oxazine that can induce apoptosis by targeting NF-κB in hepatocellular carcinoma cells |
| title_fullStr |
Identification of a novel 1,2 oxazine that can induce apoptosis by targeting NF-κB in hepatocellular carcinoma cells |
| title_full_unstemmed |
Identification of a novel 1,2 oxazine that can induce apoptosis by targeting NF-κB in hepatocellular carcinoma cells |
| title_sort |
identification of a novel 1,2 oxazine that can induce apoptosis by targeting nf-κb in hepatocellular carcinoma cells |
| publisher |
Elsevier |
| series |
Biotechnology Reports |
| issn |
2215-017X |
| publishDate |
2020-03-01 |
| description |
Constitutive 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 potently targets the NF-κB signaling pathway in HCC cells. Keywords: Oxazine, NF-κB, Anticancer, DNA fragmentation |
| url |
http://www.sciencedirect.com/science/article/pii/S2215017X19307295 |
| work_keys_str_mv |
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