Crebanine, an aporphine alkaloid, sensitizes TNF-α-induced apoptosis and suppressed invasion of human lung adenocarcinoma cells A549 by blocking NF-κB-regulated gene products

© 2014, International Society of Oncology and BioMarkers (ISOBM). Crebanine is an alkaloid known to exhibit anticancer, but its mechanism is not well understood. Besides, the nuclear factor-kappa B (NF-κB) transcription factor has been correlated with inflammation, carcinogenesis, tumor cell surviva...

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Main Authors: Supachai Yodkeeree, Wilart Pompimon, Pornngarm Limtrakul
Format: Journal
Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/53250
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spelling th-cmuir.6653943832-532502018-09-04T09:45:52Z Crebanine, an aporphine alkaloid, sensitizes TNF-α-induced apoptosis and suppressed invasion of human lung adenocarcinoma cells A549 by blocking NF-κB-regulated gene products Supachai Yodkeeree Wilart Pompimon Pornngarm Limtrakul Biochemistry, Genetics and Molecular Biology © 2014, International Society of Oncology and BioMarkers (ISOBM). Crebanine is an alkaloid known to exhibit anticancer, but its mechanism is not well understood. Besides, the nuclear factor-kappa B (NF-κB) transcription factor has been correlated with inflammation, carcinogenesis, tumor cell survival, invasion, and angiogenesis. In this study, we investigated the effects of crebanine on tumor necrosis factor alpha (TNF-α)-induced NF-κB activation and the expression of NF-κB-regulated gene products. We found that crebanine reduced the cell proliferation of lung, ovarian, and breast cancer cells. Crebanine also potentiated TNF-α-induced apoptosis which correlated with the suppression of the gene products linked to cell survival, B cell lymphoma-extra large, and proliferation, cyclin D1. In addition, crebanine affected TNF-α-induced activation of caspase-8, caspase-3, and poly(ADP-ribose) polymerase cleavage, indicating that the apoptotic effects of TNF-α were enhanced by crebanine. Moreover, crebanine reduced TNF-α-induced A549 cell invasion and migration. Furthermore, crebanine suppressed the TNF-α-mediated expression of proteins that involved cancer cell invasion (matrix metalloproteinase 9 urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and intercellular adhesion molecule 1) and angiogenesis (COX-2 and VEGF), all of which are known to be regulated by NF-κB. We also demonstrated that TNF-α induced NF-κB DNA-binding activity, which was inhibited by crebanine. Moreover, crebanine suppressed the TNF-α-induced degradation of inhibitor of NF-κB alpha (IκBa), which led to reduced NF-κB translocation to the nucleus. Taken together, our results demonstrated that crebanine reduced TNF-α-induced cancer cell proliferation, invasion, and survival by suppressing NF-κB activity and expression profile of its downstream genes. 2018-09-04T09:45:51Z 2018-09-04T09:45:51Z 2014-01-01 Journal 14230380 10104283 2-s2.0-84919836362 10.1007/s13277-014-1998-6 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84919836362&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/53250
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Biochemistry, Genetics and Molecular Biology
spellingShingle Biochemistry, Genetics and Molecular Biology
Supachai Yodkeeree
Wilart Pompimon
Pornngarm Limtrakul
Crebanine, an aporphine alkaloid, sensitizes TNF-α-induced apoptosis and suppressed invasion of human lung adenocarcinoma cells A549 by blocking NF-κB-regulated gene products
description © 2014, International Society of Oncology and BioMarkers (ISOBM). Crebanine is an alkaloid known to exhibit anticancer, but its mechanism is not well understood. Besides, the nuclear factor-kappa B (NF-κB) transcription factor has been correlated with inflammation, carcinogenesis, tumor cell survival, invasion, and angiogenesis. In this study, we investigated the effects of crebanine on tumor necrosis factor alpha (TNF-α)-induced NF-κB activation and the expression of NF-κB-regulated gene products. We found that crebanine reduced the cell proliferation of lung, ovarian, and breast cancer cells. Crebanine also potentiated TNF-α-induced apoptosis which correlated with the suppression of the gene products linked to cell survival, B cell lymphoma-extra large, and proliferation, cyclin D1. In addition, crebanine affected TNF-α-induced activation of caspase-8, caspase-3, and poly(ADP-ribose) polymerase cleavage, indicating that the apoptotic effects of TNF-α were enhanced by crebanine. Moreover, crebanine reduced TNF-α-induced A549 cell invasion and migration. Furthermore, crebanine suppressed the TNF-α-mediated expression of proteins that involved cancer cell invasion (matrix metalloproteinase 9 urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and intercellular adhesion molecule 1) and angiogenesis (COX-2 and VEGF), all of which are known to be regulated by NF-κB. We also demonstrated that TNF-α induced NF-κB DNA-binding activity, which was inhibited by crebanine. Moreover, crebanine suppressed the TNF-α-induced degradation of inhibitor of NF-κB alpha (IκBa), which led to reduced NF-κB translocation to the nucleus. Taken together, our results demonstrated that crebanine reduced TNF-α-induced cancer cell proliferation, invasion, and survival by suppressing NF-κB activity and expression profile of its downstream genes.
format Journal
author Supachai Yodkeeree
Wilart Pompimon
Pornngarm Limtrakul
author_facet Supachai Yodkeeree
Wilart Pompimon
Pornngarm Limtrakul
author_sort Supachai Yodkeeree
title Crebanine, an aporphine alkaloid, sensitizes TNF-α-induced apoptosis and suppressed invasion of human lung adenocarcinoma cells A549 by blocking NF-κB-regulated gene products
title_short Crebanine, an aporphine alkaloid, sensitizes TNF-α-induced apoptosis and suppressed invasion of human lung adenocarcinoma cells A549 by blocking NF-κB-regulated gene products
title_full Crebanine, an aporphine alkaloid, sensitizes TNF-α-induced apoptosis and suppressed invasion of human lung adenocarcinoma cells A549 by blocking NF-κB-regulated gene products
title_fullStr Crebanine, an aporphine alkaloid, sensitizes TNF-α-induced apoptosis and suppressed invasion of human lung adenocarcinoma cells A549 by blocking NF-κB-regulated gene products
title_full_unstemmed Crebanine, an aporphine alkaloid, sensitizes TNF-α-induced apoptosis and suppressed invasion of human lung adenocarcinoma cells A549 by blocking NF-κB-regulated gene products
title_sort crebanine, an aporphine alkaloid, sensitizes tnf-α-induced apoptosis and suppressed invasion of human lung adenocarcinoma cells a549 by blocking nf-κb-regulated gene products
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84919836362&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/53250
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