{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:36:24Z","timestamp":1791401784409,"version":"4.3.3"},"reference-count":102,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Although the effect of thymoquinone (TQ), the biologically active component of black cumin seeds, has been investigated in many types of cancer, its effects on molecular pathways of cancer cells further need to be elucidated. This study aimed to investigate the effects of TQ on genotoxicity, oxidative stress, apoptosis, and inflammatory pathways in SW620 cells treated with irinotecan (IR), celecoxib (Clx), individually or both. DNA damage, oxidative stress\/inflammatory response, cell cycle, apoptosis, and expression of carcinogenesis\u2010related genes were determined using the Comet assay, ELISA assay, flow cytometry, and RT\u2010PCR techniques, respectively. TQ (8\u2009\u00b5M) combination with IR (8\u2009\u00b5M)\u2009+\u2009Clx (4\u2009\u00b5M) significantly increased cytotoxicity and genotoxicity of IR with\/without Clx, while decreasing oxidative stress and inflammatory responses. TQ upregulated p21 and Bax, while downregulating Bcl\u20102 and Bcl\u2010XL, increasing Bax\/Bcl\u20102 ratio, which indicates an induction of apoptotic pathways. TQ also increased the percentage of cells in G2\/M phase and decreased those in G0\/G1 phase, thereby affecting cell cycle checkpoints in IR\u2010treated cells with or without Clx. In conclusion, this study shows that the combination of TQ with IR, Clx, or both exerts significant effects on SW620 colon cancer cells, such that by enhancing DNA damage, TQ may induce G2\/M cell cycle arrest and apoptosis, while reducing inflammatory responses, oxidative stress, and G0\/G1 cell cycle arrest. These in vitro findings indicate that TQ may enhance the chemotherapeutic effects of IR and act as a potential adjuvant therapy; however, further in vivo studies are required to verify its suggested effects.<\/jats:p>","DOI":"10.1002\/jbt.70683","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T14:59:09Z","timestamp":1770130749000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Toxicological Effects of Thymoquinone in Combination With Celecoxib and Irinotecan on DNA Damage, Oxidative Stress, G2\/M Arrest, Apoptosis, and Inflammatory Response in SW620 Cells"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5675-2701","authenticated-orcid":false,"given":"Merve","family":"Hazar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Agri Ibrahim Cecen University A\u011fr\u0131 Turkey"},{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Hacettepe University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8581-8933","authenticated-orcid":false,"given":"Nur\u015fen","family":"Ba\u015faran","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Ba\u015fkent University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6368-2745","authenticated-orcid":false,"given":"Sevtap","family":"Aydin Dilsiz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Hacettepe University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46010010"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14040369"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1947"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120442"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2014.3223"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.10.17.16460"},{"issue":"5","key":"e_1_2_10_8_1","first-page":"34","article-title":"Effect of Metformin on Irinotecan\u2010Induced Cell Cycle Arrest in Colorectal Cancer Cell Lines HCT116 and SW480","volume":"15","author":"Khader E. I.","year":"2021","journal-title":"International Journal of Health Sciences"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/6231095"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.22268"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-023-02288-z"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/1735-5362.199049"},{"issue":"2","key":"e_1_2_10_13_1","first-page":"68","article-title":"The Effect of Celecoxib and Its Combination With Imatinib on Human HT\u201029 Colorectal Cancer Cells: Involvement of COX\u20102, Caspase\u20103, VEGF and NF\u2010\u03baB Genes Expression","volume":"62","author":"Atari\u2010Hajipirloo S.","year":"2016","journal-title":"Cellular and Molecular Biology"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2014.3543"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2020.12.026"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2021.07.013"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00295"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-023-03174-4"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.08.021"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.70276"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.70238"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368910x508988"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.26650\/IstanbulJPharm.2022.1105443"},{"issue":"2","key":"e_1_2_10_24_1","first-page":"479","article-title":"In Vitro Synergistic Antitumor Activity of a Combination of 5\u2010Fluorouracil and Irinotecan in Human Colon Cancer","volume":"28","author":"Inoue Y.","year":"2006","journal-title":"International Journal of Oncology"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2003.12.014"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22770"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200038030-00003"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.4274\/tjps.galenos.2023.60543"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.09.029"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3831\/kpi.2017.20.019"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2018.4514"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2013.02.002"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12938-022-01012-8"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23315"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6342"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14091730"},{"issue":"2","key":"e_1_2_10_37_1","first-page":"103","article-title":"Antiproliferative Effect of Thymoquinone on Human Colon Cancer Cells: Is It Dependent on Glycolytic Pathway?","volume":"14","author":"\u00d6zko\u00e7 M.","year":"2023","journal-title":"Acibadem Universitesi Saglik Bilimleri Dergisi"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.4971"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i7.1171"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdf337"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.477"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2018.02.136"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202301886"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.Can-08-0884"},{"issue":"4","key":"e_1_2_10_45_1","first-page":"857","article-title":"Thymoquinone Extracted From Black Seed Triggers Apoptotic Cell Death in Human Colorectal Cancer Cells via a p53\u2010Dependent Mechanism","volume":"25","author":"Gali\u2010Muhtasib H.","year":"2004","journal-title":"International Journal of Oncology"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1558289"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01398-5"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00026.2013"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.23993"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-05-0171"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2018.05.013"},{"key":"e_1_2_10_52_1","first-page":"357","article-title":"The Physiological Effect of Conventional Treatment With Epigallocatechin\u20103\u2010Gallate, Thymoquinone, and Tannic Acid on the LNCaP Cell Line","volume":"42","author":"Richards L. R.","year":"2006","journal-title":"Biomedical Sciences Instrumentation"},{"key":"e_1_2_10_53_1","first-page":"363","article-title":"Effects of (\u2010)Epigallocatechin Gallate and Thymoquinone on Proliferation of a PANC\u20101 Cell Line in Culture","volume":"42","author":"Tan M.","year":"2006","journal-title":"Biomedical Sciences Instrumentation"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1081\/dct-120020404"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1006\/phrs.1999.0585"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075356"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2010.009369"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-009-0421-z"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.22822"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2010.509832"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.59566\/IJBS.2007.3176"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.12.002"},{"issue":"9","key":"e_1_2_10_63_1","first-page":"2323","article-title":"Inducible Chemoresistance to 7\u2010Ethyl\u201010\u2010[4\u2010(1\u2010Piperidino)\u20101\u2010Piperidino]\u2010Carbonyloxycamptothe Cin (CPT\u201011) in Colorectal Cancer Cells and a Xenograft Model Is Overcome by Inhibition of Nuclear Factor\u2010KappaB Activation","volume":"60","author":"Cusack JC Jr","year":"2000","journal-title":"Cancer Research"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.08.042"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2014.2513"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-03-0366"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0959-8049(99)00222-1"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.14715\/cmb\/2018.64.7.2"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-012-9469-4"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-010-0051-7"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.01.024"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1734-1140(11)70641-7"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1477-2574.2009.00059.x"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126830"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16828"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0299fje"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.107.047886"},{"issue":"9","key":"e_1_2_10_78_1","first-page":"3535","article-title":"Enhanced Chemosensitivity to CPT\u201011 With Proteasome Inhibitor PS\u2010341: Implications for Systemic Nuclear Factor\u2010Kappab Inhibition","volume":"61","author":"Cusack JC Jr","year":"2001","journal-title":"Cancer Research"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.122.001118"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.12.033"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-5793(02)03535-4"},{"issue":"21","key":"e_1_2_10_82_1","first-page":"6045","article-title":"Celecoxib Prevents Tumor Growth In Vivo Without Toxicity to Normal Gut: Lack of Correlation Between In Vitro and In Vivo Models","volume":"60","author":"Williams C. S.","year":"2000","journal-title":"Cancer Research"},{"issue":"5","key":"e_1_2_10_83_1","first-page":"3229","article-title":"A Celecoxib Derivative Potently Inhibits Proliferation of Colon Adenocarcinoma Cells by Induction of Apoptosis","volume":"26","author":"Kusunoki N.","year":"2006","journal-title":"Anticancer Research"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1177\/1534735419901160"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf5054063"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11040879"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25030658"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2009.954446"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.Can-04-2488"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.1593\/tlo.10124"},{"issue":"4","key":"e_1_2_10_91_1","first-page":"3099","article-title":"Mutant p53 Mediated Induction of Cell Cycle Arrest and Apoptosis at G1 Phase by 9\u2010Hydroxyellipticine","volume":"19","author":"Sugikawa E.","year":"1999","journal-title":"Anticancer Research"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.06.033"},{"key":"e_1_2_10_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401916"},{"key":"e_1_2_10_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01676-z"},{"key":"e_1_2_10_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01608-z"},{"key":"e_1_2_10_96_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04196-2"},{"key":"e_1_2_10_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204264"},{"key":"e_1_2_10_98_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo_00000418"},{"key":"e_1_2_10_99_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201119200"},{"key":"e_1_2_10_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2011.09.005"},{"key":"e_1_2_10_101_1","doi-asserted-by":"publisher","DOI":"10.16984\/saufenbilder.585012"},{"key":"e_1_2_10_102_1","first-page":"495","article-title":"From Here to Eternity\u2014The Secret of Pharaohs: Therapeutic Potential of Black Cumin Seeds and Beyond","volume":"6","author":"Padhye S.","year":"2008","journal-title":"Cancer Therapy"},{"key":"e_1_2_10_103_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29245907"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70683","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70683","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70683","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T09:33:55Z","timestamp":1771234435000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":102,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/jbt.70683"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70683","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70683"}}