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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2019-01-01
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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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institution | Kabale University |
issn | 2210-7177 2210-7185 |
language | English |
publishDate | 2019-01-01 |
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series | Analytical Cellular Pathology |
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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