Gene Ontology and Expression Studies of Strigolactone Analogues on a Hepatocellular Carcinoma Cell Line

Human hepatocellular carcinoma (HCC) is the most common and recurrent type of primary adult liver cancer without any effective therapy. Plant-derived compounds acting as anticancer agents can induce apoptosis by targeting several signaling pathways. Strigolactone (SL) is a novel class of phytohormon...

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Main Authors: Mohammed Nihal Hasan, Syed Shoeb Razvi, Hani Choudhry, Mohammed A. Hassan, Said Salama Moselhy, Taha Abduallah Kumosani, Mazin A. Zamzami, Khalid Omer Abualnaja, Majed A. Halwani, Abdulrahman Labeed Al-Malki, Jiannis Ragoussis, Wei Wu, Christian Bronner, Tadao Asami, Mahmoud Alhosin
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Analytical Cellular Pathology
Online Access:http://dx.doi.org/10.1155/2019/1598182
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author Mohammed Nihal Hasan
Syed Shoeb Razvi
Hani Choudhry
Mohammed A. Hassan
Said Salama Moselhy
Taha Abduallah Kumosani
Mazin A. Zamzami
Khalid Omer Abualnaja
Majed A. Halwani
Abdulrahman Labeed Al-Malki
Jiannis Ragoussis
Wei Wu
Christian Bronner
Tadao Asami
Mahmoud Alhosin
author_facet Mohammed Nihal Hasan
Syed Shoeb Razvi
Hani Choudhry
Mohammed A. Hassan
Said Salama Moselhy
Taha Abduallah Kumosani
Mazin A. Zamzami
Khalid Omer Abualnaja
Majed A. Halwani
Abdulrahman Labeed Al-Malki
Jiannis Ragoussis
Wei Wu
Christian Bronner
Tadao Asami
Mahmoud Alhosin
author_sort Mohammed Nihal Hasan
collection DOAJ
description Human hepatocellular carcinoma (HCC) is the most common and recurrent type of primary adult liver cancer without any effective therapy. Plant-derived compounds acting as anticancer agents can induce apoptosis by targeting several signaling pathways. Strigolactone (SL) is a novel class of phytohormone, whose analogues have been reported to possess anticancer properties on a panel of human cancer cell lines through inducing cell cycle arrest, destabilizing microtubular integrity, reducing damaged in the DNA repair machinery, and inducing apoptosis. In our previous study, we reported that a novel SL analogue, TIT3, reduces HepG2 cell proliferation, inhibits cell migration, and induces apoptosis. To decipher the mechanisms of TIT3-induced anticancer activity in HepG2, we performed RNA sequencing and the differential expression of genes was analyzed using different tools. RNA-Seq data showed that the genes responsible for microtubule organization such as TUBB, BUB1B, TUBG2, TUBGCP6, TPX2, and MAP7 were significantly downregulated. Several epigenetic modulators such as UHRF1, HDAC7, and DNMT1 were also considerably downregulated, and this effect was associated with significant upregulation of various proapoptotic genes including CASP3, TNF-α, CASP7, and CDKN1A (p21). Likewise, damaged DNA repair genes such as RAD51, RAD52, and DDB2 were also significantly downregulated. This study indicates that TIT3-induced antiproliferative and proapoptotic activities on HCC cells could involve several signaling pathways. Our results suggest that TIT3 might be a promising drug to treat HCC.
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spelling doaj-art-67ddb86546b9474da94b6e129aa5e2402025-02-03T05:45:54ZengWileyAnalytical Cellular Pathology2210-71772210-71852019-01-01201910.1155/2019/15981821598182Gene Ontology and Expression Studies of Strigolactone Analogues on a Hepatocellular Carcinoma Cell LineMohammed Nihal Hasan0Syed Shoeb Razvi1Hani Choudhry2Mohammed A. Hassan3Said Salama Moselhy4Taha Abduallah Kumosani5Mazin A. Zamzami6Khalid Omer Abualnaja7Majed A. Halwani8Abdulrahman Labeed Al-Malki9Jiannis Ragoussis10Wei Wu11Christian Bronner12Tadao Asami13Mahmoud Alhosin14Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaNanomedicine Department, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Human Genetics, McGill University, Montréal, QC, H3A 0C7, CanadaDepartment of Medicine, University of California, San Francisco, CA 94143, USAInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258 CNRS UMR 7104, Université de Strasbourg, Illkirch, FranceDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi ArabiaHuman hepatocellular carcinoma (HCC) is the most common and recurrent type of primary adult liver cancer without any effective therapy. Plant-derived compounds acting as anticancer agents can induce apoptosis by targeting several signaling pathways. Strigolactone (SL) is a novel class of phytohormone, whose analogues have been reported to possess anticancer properties on a panel of human cancer cell lines through inducing cell cycle arrest, destabilizing microtubular integrity, reducing damaged in the DNA repair machinery, and inducing apoptosis. In our previous study, we reported that a novel SL analogue, TIT3, reduces HepG2 cell proliferation, inhibits cell migration, and induces apoptosis. To decipher the mechanisms of TIT3-induced anticancer activity in HepG2, we performed RNA sequencing and the differential expression of genes was analyzed using different tools. RNA-Seq data showed that the genes responsible for microtubule organization such as TUBB, BUB1B, TUBG2, TUBGCP6, TPX2, and MAP7 were significantly downregulated. Several epigenetic modulators such as UHRF1, HDAC7, and DNMT1 were also considerably downregulated, and this effect was associated with significant upregulation of various proapoptotic genes including CASP3, TNF-α, CASP7, and CDKN1A (p21). Likewise, damaged DNA repair genes such as RAD51, RAD52, and DDB2 were also significantly downregulated. This study indicates that TIT3-induced antiproliferative and proapoptotic activities on HCC cells could involve several signaling pathways. Our results suggest that TIT3 might be a promising drug to treat HCC.http://dx.doi.org/10.1155/2019/1598182
spellingShingle Mohammed Nihal Hasan
Syed Shoeb Razvi
Hani Choudhry
Mohammed A. Hassan
Said Salama Moselhy
Taha Abduallah Kumosani
Mazin A. Zamzami
Khalid Omer Abualnaja
Majed A. Halwani
Abdulrahman Labeed Al-Malki
Jiannis Ragoussis
Wei Wu
Christian Bronner
Tadao Asami
Mahmoud Alhosin
Gene Ontology and Expression Studies of Strigolactone Analogues on a Hepatocellular Carcinoma Cell Line
Analytical Cellular Pathology
title Gene Ontology and Expression Studies of Strigolactone Analogues on a Hepatocellular Carcinoma Cell Line
title_full Gene Ontology and Expression Studies of Strigolactone Analogues on a Hepatocellular Carcinoma Cell Line
title_fullStr Gene Ontology and Expression Studies of Strigolactone Analogues on a Hepatocellular Carcinoma Cell Line
title_full_unstemmed Gene Ontology and Expression Studies of Strigolactone Analogues on a Hepatocellular Carcinoma Cell Line
title_short Gene Ontology and Expression Studies of Strigolactone Analogues on a Hepatocellular Carcinoma Cell Line
title_sort gene ontology and expression studies of strigolactone analogues on a hepatocellular carcinoma cell line
url http://dx.doi.org/10.1155/2019/1598182
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