{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:05:14Z","timestamp":1790690714540,"version":"4.1.0"},"reference-count":112,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21804144"],"award-info":[{"award-number":["21804144"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073799"],"award-info":[{"award-number":["82073799"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U1903125"],"award-info":[{"award-number":["U1903125"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2022,4]]},"DOI":"10.1016\/j.phymed.2022.153936","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T01:50:35Z","timestamp":1642384235000},"page":"153936","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"special_numbering":"C","title":["Combinatorial effect of thymoquinone with chemo agents for tumor therapy"],"prefix":"10.1016","volume":"98","author":[{"given":"Shah","family":"Jehan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umar","family":"Farooq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irum","family":"Basheer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2022.153936_bib0001","doi-asserted-by":"crossref","first-page":"41","DOI":"10.4103\/1110-208X.170558","article-title":"Protective effect of Nigella sativa against cerebral ischemia and sodium valproate-induced hepatotoxicity","volume":"32","author":"Abd El Latif","year":"2015","journal-title":"Benha Med. J."},{"key":"10.1016\/j.phymed.2022.153936_bib0002","first-page":"25","article-title":"Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats","volume":"20","author":"Al-Ali","year":"2008","journal-title":"J. Ayub Med. Coll. Abbottabad"},{"key":"10.1016\/j.phymed.2022.153936_bib0003","first-page":"107","article-title":"Phase I safety and clinical activity study of thymoquinone in pa-tients with advanced refractory malignant disease","volume":"10","author":"Al-Amri","year":"2009","journal-title":"Shiraz E Med. J."},{"key":"10.1016\/j.phymed.2022.153936_bib0004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1472-6882-14-282","article-title":"Thymoquinone attenuates cisplatin-induced hepatotoxicity via nuclear factor kappa-\u03b2","volume":"14","author":"Al-Malki","year":"2014","journal-title":"BMC Complement. Altern. Med."},{"key":"10.1016\/j.phymed.2022.153936_bib0005","first-page":"193","article-title":"Thymoquinone protects against doxorubicin-induced cardiotoxicity without compromising its antitumor activity","volume":"17","author":"Al-Shabanah","year":"1998","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"10.1016\/j.phymed.2022.153936_bib0006","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.bcp.2009.12.015","article-title":"Induction of apoptosis by thymoquinone in lymphoblastic leukemia Jurkat cells is mediated by a p73-dependent pathway which targets the epigenetic integrator UHRF1","volume":"79","author":"Alhosin","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.phymed.2022.153936_bib0007","doi-asserted-by":"crossref","DOI":"10.1177\/1533033820947489","article-title":"Thymoquinone and difluoromethylornithine (DFMO) synergistically induce apoptosis of human acute T lymphoblastic leukemia jurkat cells through the modulation of epigenetic pathways","volume":"19","author":"Alhosin","year":"2020","journal-title":"Technol. Cancer Res. Treat."},{"key":"10.1016\/j.phymed.2022.153936_bib0008","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1177\/1535370215579013","article-title":"The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles","volume":"240","author":"Ali","year":"2015","journal-title":"Exp. Biol. Med."},{"key":"10.1016\/j.phymed.2022.153936_bib0009","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s13318-014-0207-8","article-title":"Pharmacokinetic plasma behaviors of intravenous and oral bioavailability of thymoquinone in a rabbit model","volume":"40","author":"Alkharfy","year":"2015","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"10.1016\/j.phymed.2022.153936_bib0010","doi-asserted-by":"crossref","DOI":"10.1002\/bab.2062","article-title":"Thymoquinone inhibits IL-7-induced tumor progression and metastatic invasion in prostate cancer cells by attenuating matrix metalloproteinase activity and Akt\/NF-\u03baB signaling","author":"Alshyarba","year":"2020","journal-title":"Biotechnol. Appl. Biochem."},{"key":"10.1016\/j.phymed.2022.153936_bib0011","first-page":"28","article-title":"Thymoquinone up-regulates PTEN expression and induces apoptosis in doxorubicin-resistant human breast cancer cells","volume":"706","author":"Arafa","year":"2011","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen."},{"key":"10.1016\/j.phymed.2022.153936_bib0012","first-page":"207","article-title":"Hepatoprotective natural products","volume":"55","author":"Bachara","year":"2020","journal-title":"Med. Nat. Prod. Dis. Focus. Approach"},{"key":"10.1016\/j.phymed.2022.153936_bib0013","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0023741","article-title":"Thymoquinone inhibits the CXCL12-induced chemotaxis of multiple myeloma cells and increases their susceptibility to Fas-mediated apoptosis","volume":"6","author":"Badr","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.phymed.2022.153936_bib0014","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1080\/01635581.2010.509832","article-title":"Review on molecular and therapeutic potential of thymoquinone in cancer","volume":"62","author":"Banerjee","year":"2010","journal-title":"Nutr. Cancer"},{"key":"10.1016\/j.phymed.2022.153936_bib0015","first-page":"434","article-title":"Effects of thymoquinone and selenium on the proliferation of mg 63 cells in tissue culture","volume":"44","author":"Barron","year":"2008","journal-title":"Biomed. Sci. Instrum."},{"key":"10.1016\/j.phymed.2022.153936_bib0016","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-30046-z","article-title":"Thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities","volume":"8","author":"Bashmail","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.phymed.2022.153936_bib0017","doi-asserted-by":"crossref","DOI":"10.1002\/cncr.33587","article-title":"The ever-increasing importance of cancer as a leading cause of premature death worldwide","author":"Bray","year":"2021","journal-title":"Cancer"},{"key":"10.1016\/j.phymed.2022.153936_bib0018","series-title":"The Effects of Thymoquinone and Doxorubicin on Leukemia and Cardiomyocyte Cell Lines","author":"Brown","year":"2014"},{"key":"10.1016\/j.phymed.2022.153936_bib0019","doi-asserted-by":"crossref","first-page":"625","DOI":"10.3390\/nu9060625","article-title":"Role of Nigella sativa and its constituent thymoquinone on chemotherapy-induced nephrotoxicity: evidences from experimental animal studies","volume":"9","author":"Cascella","year":"2017","journal-title":"Nutrients"},{"key":"10.1016\/j.phymed.2022.153936_bib0020","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/j.1477-2574.2009.00059.x","article-title":"Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells","volume":"11","author":"Chehl","year":"2009","journal-title":"HPB"},{"key":"10.1016\/j.phymed.2022.153936_bib0021","series-title":"Glossary of Indian medicinal Plants","author":"Chopra","year":"1956"},{"key":"10.1016\/j.phymed.2022.153936_bib0022","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000443404","article-title":"Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents","volume":"25","author":"Cragg","year":"2016","journal-title":"Med. Princ. Pract."},{"key":"10.1016\/j.phymed.2022.153936_bib0023","first-page":"309","article-title":"Cardiotoxicity of anticancer treatments: epidemiology, detection, and management","volume":"66","author":"Curigliano","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.phymed.2022.153936_bib0024","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S1471-4892(01)00063-7","article-title":"Natural products in anticancer therapy","volume":"1","author":"Da Rocha","year":"2001","journal-title":"Curr. Opin. Pharmacol."},{"key":"10.1016\/j.phymed.2022.153936_bib0025","doi-asserted-by":"crossref","first-page":"e46641","DOI":"10.1371\/journal.pone.0046641","article-title":"Antineoplastic and apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinoma","volume":"7","author":"Das","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.phymed.2022.153936_bib0026","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s12272-020-01241-2","article-title":"Indirubin-3-monoxime and thymoquinone exhibit synergistic efficacy as therapeutic combination in in-vitro and in-vivo models of Lung cancer","volume":"43","author":"Dera","year":"2020","journal-title":"Arch. Pharm. Res."},{"key":"10.1016\/j.phymed.2022.153936_bib0027","doi-asserted-by":"crossref","first-page":"706","DOI":"10.2741\/E651","article-title":"Thymoquinone induces apoptosis in malignant T-cells via generation of ROS","volume":"5","author":"Dergarabetian","year":"2013","journal-title":"Front. Biosci."},{"key":"10.1016\/j.phymed.2022.153936_bib0028","first-page":"1055","article-title":"Enhanced cytotoxicity and apoptosis by thymoquinone in combination with zoledronic acid in hormone-and drug-resistant prostate cancer cell lines","volume":"19","author":"Dirican","year":"2014","journal-title":"J. BUON"},{"key":"10.1016\/j.phymed.2022.153936_bib0029","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s00280-010-1386-x","article-title":"Combinatorial effects of thymoquinone on the anti-cancer activity of doxorubicin","volume":"67","author":"Effenberger-Neidnicht","year":"2011","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.phymed.2022.153936_bib0030","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/cbdv.200900328","article-title":"Terpene conjugates of the Nigella sativa seed-oil constituent thymoquinone with enhanced efficacy in cancer cells","volume":"7","author":"Effenberger","year":"2010","journal-title":"Chem. Biodivers."},{"key":"10.1016\/j.phymed.2022.153936_bib0031","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s10495-009-0421-z","article-title":"Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling","volume":"15","author":"El-Najjar","year":"2010","journal-title":"Apoptosis"},{"key":"10.1016\/j.phymed.2022.153936_bib0032","first-page":"2015","article-title":"Mechanisms of thymoquinone hepatorenal protection in methotrexate-induced toxicity in rats","author":"El-Sheikh","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"10.1016\/j.phymed.2022.153936_bib0033","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.cbi.2014.09.015","article-title":"Thymoquinone attenuates doxorubicin-induced nephrotoxicity in rats: role of Nrf2 and NOX4","volume":"223","author":"Elsherbiny","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.phymed.2022.153936_bib0034","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1007\/s00210-019-01688-1","article-title":"In vitro study of the cytotoxicity of thymoquinone\/curcumin fluorescent liposomes","volume":"392","author":"Fahmy","year":"2019","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"10.1016\/j.phymed.2022.153936_bib0035","first-page":"359","article-title":"Effect of Nigella sativa (N. sativa L.) and oxidative stress on the survival pattern of MCF-7 breast cancer cells","volume":"39","author":"Farah","year":"2003","journal-title":"Biomed. Sci. Instrum."},{"key":"10.1016\/j.phymed.2022.153936_bib0036","first-page":"1","article-title":"Thymoquinone potentiated the anticancer effect of cisplatin on hepatic tumorigenesis by modulating tissue oxidative stress and endoplasmic GRP78\/CHOP signaling","author":"Farghaly","year":"2021","journal-title":"Nutr. Cancer"},{"key":"10.1016\/j.phymed.2022.153936_bib0037","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2019.116628","article-title":"Thymoquinone enhances the anticancer activity of doxorubicin against adult T-cell leukemia in vitro and in vivo through ROS-dependent mechanisms","volume":"232","author":"Fatfat","year":"2019","journal-title":"Life Sci."},{"key":"10.1016\/j.phymed.2022.153936_bib0038","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.biocel.2005.10.009","article-title":"Thymoquinone: a promising anti-cancer drug from natural sources","volume":"38","author":"Gali-Muhtasib","year":"2006","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"10.1016\/j.phymed.2022.153936_bib0039","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1097\/00001813-200404000-00012","article-title":"Molecular pathway for thymoquinone-induced cell-cycle arrest and apoptosis in neoplastic keratinocytes","volume":"15","author":"Gali-Muhtasib","year":"2004","journal-title":"Anticancer Drugs"},{"key":"10.1016\/j.phymed.2022.153936_bib0040","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1111\/j.1582-4934.2007.00095.x","article-title":"Thymoquinone reduces mouse colon tumor cell invasion and inhibits tumor growth in murine colon cancer models","volume":"12","author":"Gali-Muhtasib","year":"2008","journal-title":"J. Cell. Mol. Med."},{"key":"10.1016\/j.phymed.2022.153936_bib0041","first-page":"245","article-title":"Thymoquinone could increase the efficacy of tamoxifen induced apoptosis in human breast cancer cells: an in vitro study","volume":"18","author":"Ganji-Harsini","year":"2016","journal-title":"Cell J"},{"key":"10.1016\/j.phymed.2022.153936_bib0042","doi-asserted-by":"crossref","first-page":"656","DOI":"10.3389\/fphar.2017.00656","article-title":"Therapeutic potential and pharmaceutical development of thymoquinone: a multitargeted molecule of natural origin","volume":"8","author":"Goyal","year":"2017","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.phymed.2022.153936_bib0043","first-page":"225","article-title":"Thymoquinone protects against cerebral small vessel disease: role of antioxidant and anti-inflammatory activities","volume":"32","author":"Guan","year":"2018","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"10.1016\/j.phymed.2022.153936_bib0044","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.lungcan.2021.05.036","article-title":"Two cases of non-small cell lung cancer patients with somatic or germline EGFR R776H mutation","volume":"161","author":"Guo","year":"2021","journal-title":"Lung Cancer"},{"key":"10.1016\/j.phymed.2022.153936_bib0045","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jtcme.2020.04.001","article-title":"Differential effects of thymoquinone on lysophosphatidic acid-induced oncogenic pathways in ovarian cancer cells","volume":"10","author":"Ha","year":"2020","journal-title":"J. Tradit. Complement. Med."},{"key":"10.1016\/j.phymed.2022.153936_bib0046","first-page":"31","article-title":"Pathophysiological effects of thymoquinone and epigallocatechin-3-gallate on SK-OV-3 ovarian cancer like cell line","volume":"51","author":"Harpole","year":"2015","journal-title":"Biomed. Sci. Instrum."},{"key":"10.1016\/j.phymed.2022.153936_bib0047","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.117639","article-title":"Thymoquinone synergizes with arsenic and interferon alpha to target human T-cell leukemia\/lymphoma","volume":"251","author":"Houssein","year":"2020","journal-title":"Life Sci."},{"key":"10.1016\/j.phymed.2022.153936_bib0048","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s10620-017-4856-8","article-title":"Thymoquinone augments cisplatin-induced apoptosis on esophageal carcinoma through mitigating the activation of JAK2\/STAT3 pathway","volume":"63","author":"Hu","year":"2018","journal-title":"Dig. Dis. Sci."},{"key":"10.1016\/j.phymed.2022.153936_bib0049","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.freeradbiomed.2010.12.034","article-title":"Thymoquinone suppresses growth and induces apoptosis via generation of reactive oxygen species in primary effusion lymphoma","volume":"50","author":"Hussain","year":"2011","journal-title":"Free Radic. Biol."},{"key":"10.1016\/j.phymed.2022.153936_bib0050","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.fjps.2017.08.001","article-title":"Novel combination of thymoquinone and resveratrol enhances anticancer effect on hepatocellular carcinoma cell line","volume":"4","author":"Ismail","year":"2018","journal-title":"Future J. Pharm. Sci."},{"key":"10.1016\/j.phymed.2022.153936_bib0051","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/1756-9966-29-87","article-title":"Thymoquinone and cisplatin as a therapeutic combination in lung cancer: in vitro and in vivo","volume":"29","author":"Jafri","year":"2010","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"10.1016\/j.phymed.2022.153936_bib0052","first-page":"11","article-title":"Thymoquinone selectively induces hepatocellular carcinoma cell apoptosis in synergism with clinical therapeutics and dependence of p53 status","author":"Jehan","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.phymed.2022.153936_bib0053","first-page":"251","article-title":"Nephroprotective natural products","volume":"55","author":"Jivishova","year":"2020","journal-title":"Med. Nat. Prod. A Dis. Focus. Approach"},{"key":"10.1016\/j.phymed.2022.153936_bib0054","doi-asserted-by":"crossref","first-page":"6662","DOI":"10.3748\/wjg.v11.i42.6662","article-title":"Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats","volume":"11","author":"Kanter","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.phymed.2022.153936_bib0055","doi-asserted-by":"crossref","DOI":"10.1016\/j.cbi.2020.109142","article-title":"Cytotoxicity of juglone and thymoquinone against pancreatic cancer cells","volume":"327","author":"Karki","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.phymed.2022.153936_bib0056","doi-asserted-by":"crossref","first-page":"7782","DOI":"10.1158\/0008-5472.CAN-07-1483","article-title":"Androgen receptor\u2013and E2F-1\u2013targeted thymoquinone therapy for hormone-refractory prostate cancer","volume":"67","author":"Kaseb","year":"2007","journal-title":"Cancer Res."},{"key":"10.1016\/j.phymed.2022.153936_bib0057","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.2147\/DDDT.S109721","article-title":"Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats","volume":"10","author":"Kensara","year":"2016","journal-title":"Drug Des. Dev. Ther."},{"key":"10.1016\/j.phymed.2022.153936_bib0058","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1055\/s-0035-1558289","article-title":"Thymoquinone from nigella sativa seeds promotes the antitumor activity of noncytotoxic doses of topotecan in human colorectal cancer cells in vitro","volume":"82","author":"Khalife","year":"2016","journal-title":"Planta Med."},{"key":"10.1016\/j.phymed.2022.153936_bib0059","doi-asserted-by":"crossref","first-page":"S46","DOI":"10.1016\/j.clml.2014.04.014","article-title":"Antiproliferative and proapoptotic effects of topotecan in combination with thymoquinone on acute myelogenous leukemia","volume":"14","author":"Khalife","year":"2014","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"10.1016\/j.phymed.2022.153936_bib0060","first-page":"1","article-title":"Liposomal thymoquinone, a novel drug formulation: hope for lung cancer treatment","volume":"15","author":"Khan","year":"2021","journal-title":"Int. J. Health Sci."},{"key":"10.1016\/j.phymed.2022.153936_bib0061","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.31557\/APJCP.2019.20.4.1153","article-title":"Thymoquinone augments cyclophosphamide-mediated inhibition of cell proliferation in breast cancer cells","volume":"20","author":"Khan","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"10.1016\/j.phymed.2022.153936_bib0062","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1097\/00008469-200504000-00012","article-title":"Inhibition of two stage renal carcinogenesis, oxidative damage and hyperproliferative response by Nigella sativa","volume":"14","author":"Khan","year":"2005","journal-title":"Eur. J. Cancer Prev."},{"key":"10.1016\/j.phymed.2022.153936_bib0063","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1258\/ebm.2010.009369","article-title":"Studies on molecular mechanisms of growth inhibitory effects of thymoquinone against prostate cancer cells: role of reactive oxygen species","volume":"235","author":"Koka","year":"2010","journal-title":"Exp. Biol. Med."},{"key":"10.1016\/j.phymed.2022.153936_bib0064","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1007\/s10637-011-9777-3","article-title":"Thymoquinone reduces migration and invasion of human glioblastoma cells associated with FAK, MMP-2 and MMP-9 down-regulation","volume":"30","author":"Kolli-Bouhafs","year":"2012","journal-title":"Invest. New Drugs"},{"key":"10.1016\/j.phymed.2022.153936_bib0065","first-page":"22","article-title":"Mechanistic perspectives on cancer chemoprevention\/chemotherapeutic effects of thymoquinone","volume":"768","author":"Kundu","year":"2014","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen."},{"key":"10.1016\/j.phymed.2022.153936_bib0066","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.bbrc.2011.12.063","article-title":"Thymoquinone inhibits growth and augments 5-fluorouracil-induced apoptosis in gastric cancer cells both in vitro and in vivo","volume":"417","author":"Lei","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.phymed.2022.153936_bib0067","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/j.1476-5381.2010.00874.x","article-title":"Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway","volume":"161","author":"Li","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.phymed.2022.153936_bib0068","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.3390\/molecules22122105","article-title":"Thymoquinone inhibits the migration and invasive characteristics of cervical cancer cells SiHa and CaSki in vitro by targeting epithelial to mesenchymal transition associated transcription factors Twist1 and Zeb1","volume":"22","author":"Li","year":"2017","journal-title":"Molecules"},{"key":"10.1016\/j.phymed.2022.153936_bib0069","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.biopha.2018.02.055","article-title":"Quercetin enhances chemotherapeutic effect of doxorubicin against human breast cancer cells while reducing toxic side effects of it","volume":"100","author":"Li","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.phymed.2022.153936_bib0070","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.jclinepi.2009.06.006","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration","volume":"62","author":"Liberati","year":"2009","journal-title":"J. Clin. Epidemiol."},{"key":"10.1016\/j.phymed.2022.153936_bib0071","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0378-8741(92)90023-K","article-title":"Medicinal plants in a Middle Paleolithic grave Shanidar IV?","volume":"35","author":"Lietava","year":"1992","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2022.153936_bib0072","doi-asserted-by":"crossref","first-page":"12206","DOI":"10.1007\/s11356-016-6419-5","article-title":"Protective effect of thymoquinone against lead-induced hepatic toxicity in rats","volume":"23","author":"Mabrouk","year":"2016","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"10.1016\/j.phymed.2022.153936_bib0073","doi-asserted-by":"crossref","first-page":"3911","DOI":"10.1080\/10408398.2016.1277971","article-title":"Anti-cancer properties and mechanisms of action of thymoquinone, the major active ingredient of Nigella sativa","volume":"57","author":"Majdalawieh","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"10.1016\/j.phymed.2022.153936_bib0074","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.3390\/molecules21081055","article-title":"The role of natural polyphenols in the prevention and treatment of cervical cancer\u2014an overview","volume":"21","author":"Moga","year":"2016","journal-title":"Molecules"},{"key":"10.1016\/j.phymed.2022.153936_bib0075","doi-asserted-by":"crossref","first-page":"281","DOI":"10.2174\/1871520611313020015","article-title":"Combinations of plant polyphenols & anti-cancer molecules: a novel treatment strategy for cancer chemotherapy","volume":"13","author":"Mohan","year":"2013","journal-title":"Anticancer Agents Med. Chem."},{"key":"10.1016\/j.phymed.2022.153936_bib0076","unstructured":"Nadkarni, K., 1976. Crocus sativus, Nigella sativa. Indian materia medica Bombay, Popular Prakashan, 386\u2013411."},{"key":"10.1016\/j.phymed.2022.153936_bib0077","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/jbt.20369","article-title":"Thymoquinone supplementation attenuates cyclophosphamide-induced cardiotoxicity in rats","volume":"25","author":"Nagi","year":"2011","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"10.1016\/j.phymed.2022.153936_bib0078","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/j.tiv.2011.04.030","article-title":"Thymoquinone from Nigella sativa was more potent than cisplatin in eliminating of SiHa cells via apoptosis with down-regulation of Bcl-2 protein","volume":"25","author":"Ng","year":"2011","journal-title":"Toxicol. In Vitro"},{"key":"10.1016\/j.phymed.2022.153936_bib0079","doi-asserted-by":"crossref","first-page":"324","DOI":"10.4103\/0973-1482.235349","article-title":"Synergistic effect of thymoquinone and melatonin against breast cancer implanted in mice","volume":"14","author":"Odeh","year":"2018","journal-title":"J. Cancer Res. Ther."},{"key":"10.1016\/j.phymed.2022.153936_bib0080","doi-asserted-by":"crossref","first-page":"5905","DOI":"10.2147\/IJN.S114205","article-title":"Acute and subacute toxicity profiles of thymoquinone-loaded nanostructured lipid carrier in BALB\/c mice","volume":"11","author":"Ong","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"10.1016\/j.phymed.2022.153936_bib0081","series-title":"Nephrotoxicity from Chemotherapeutic Agents: Clinical Manifestations, Pathobiology, and Prevention\/therapy, Seminars in Nephrology","first-page":"570","author":"Perazella","year":"2010"},{"key":"10.1016\/j.phymed.2022.153936_bib0082","first-page":"1215","article-title":"The effect of thymoquinone, an active component of Nigella sativa, on isoproterenol induced myocardial injury","volume":"26","author":"Randhawa","year":"2013","journal-title":"Pak. J. Pharm. Sci."},{"key":"10.1016\/j.phymed.2022.153936_bib0083","doi-asserted-by":"crossref","DOI":"10.1016\/j.fct.2021.112604","article-title":"Thymoquinone induces oxidative stress-mediated apoptosis through downregulation of Jak2\/STAT3 signaling pathway in human melanoma cells","volume":"157","author":"Raut","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.phymed.2022.153936_bib0084","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1016\/j.bcp.2010.01.023","article-title":"Thymoquinone poly (lactide-co-glycolide) nanoparticles exhibit enhanced anti-proliferative, anti-inflammatory, and chemosensitization potential","volume":"79","author":"Ravindran","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.phymed.2022.153936_bib0085","first-page":"04","article-title":"Protective role of food supplement Spirulina fusiformis in chemical induced hepatotoxicity: a bromobenzene model in rats","volume":"4","author":"Sabina","year":"2014","journal-title":"Int. J. Pharm. Res."},{"key":"10.1016\/j.phymed.2022.153936_bib0086","doi-asserted-by":"crossref","first-page":"4467","DOI":"10.1007\/s13277-015-4307-0","article-title":"The combination of thymoquinone and paclitaxel shows anti-tumor activity through the interplay with apoptosis network in triple-negative breast cancer","volume":"37","author":"\u015eakalar","year":"2016","journal-title":"Tumour Biol."},{"key":"10.1016\/j.phymed.2022.153936_bib0087","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.31557\/APJCP.2021.22.5.1513","article-title":"Combination therapy of TRAIL and thymoquinone induce breast cancer cell cytotoxicity-mediated apoptosis and cell cycle arrest","volume":"22","author":"Salam","year":"2021","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"10.1016\/j.phymed.2022.153936_bib0088","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1207\/S15327914NC4502_09","article-title":"Chemopreventive potential of volatile oil from black cumin (Nigella sativa L.) seeds against rat colon carcinogenesis","volume":"45","author":"Salim","year":"2003","journal-title":"Nutr. Cancer"},{"key":"10.1016\/j.phymed.2022.153936_bib0089","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/01635589109514142","article-title":"Inhibitory effects of Nigella sativa and saffron (Crocus sativus) on chemical carcinogenesis in mice","volume":"16","author":"Salomi","year":"1991","journal-title":"Nutr. Cancer"},{"key":"10.1016\/j.phymed.2022.153936_bib0090","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.3390\/cancers11091390","article-title":"Docetaxel combined with thymoquinone induces apoptosis in prostate cancer cells via inhibition of the PI3K\/AKT signaling pathway","volume":"11","author":"Singh","year":"2019","journal-title":"Cancers"},{"key":"10.1016\/j.phymed.2022.153936_bib0091","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1139\/cjpp-2014-0148","article-title":"Protective role of thymoquinone against liver damage induced by tamoxifen in female rats","volume":"92","author":"Suddek","year":"2014","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"10.1016\/j.phymed.2022.153936_bib0092","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s10787-012-0160-6","article-title":"Thymoquinone attenuates cyclophosphamide-induced pulmonary injury in rats","volume":"21","author":"Suddek","year":"2013","journal-title":"Inflammopharmacology"},{"key":"10.1016\/j.phymed.2022.153936_bib0093","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1080\/01635581.2012.630551","article-title":"Cancer cell signaling pathways targeted by spice-derived nutraceuticals","volume":"64","author":"Sung","year":"2012","journal-title":"Nutr. Cancer"},{"key":"10.1016\/j.phymed.2022.153936_bib0094","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.phymed.2022.153936_bib0095","doi-asserted-by":"crossref","first-page":"350","DOI":"10.2174\/1573406415666190416165732","article-title":"Molecular docking and dynamics simulation analysis of thymoquinone and thymol compounds from nigella sativa L. that inhibits P38 protein: probable remedies for hepatocellular carcinoma","volume":"16","author":"Tabassum","year":"2020","journal-title":"Med. Chem."},{"key":"10.1016\/j.phymed.2022.153936_bib0096","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3390\/scipharm85030027","article-title":"Regressions of breast carcinoma syngraft following treatment with piperine in combination with thymoquinone","volume":"85","author":"Talib","year":"2017","journal-title":"Sci. Pharm."},{"key":"10.1016\/j.phymed.2022.153936_bib0097","doi-asserted-by":"crossref","first-page":"519","DOI":"10.3797\/scipharm.1211-15","article-title":"Combinatorial effects of thymoquinone on the anticancer activity and hepatotoxicity of the prodrug CB 1954","volume":"81","author":"Talib","year":"2013","journal-title":"Sci. Pharm."},{"key":"10.1016\/j.phymed.2022.153936_bib0098","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1097\/MEG.0b013e3283603e89","article-title":"Herbal hepatotoxicity: suspected cases assessed for alternative causes","volume":"25","author":"Teschke","year":"2013","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"10.1016\/j.phymed.2022.153936_bib0099","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.lfs.2005.01.022","article-title":"Cytotoxic effects of a decoction of Nigella sativa, Hemidesmus indicus and Smilax glabra on human hepatoma HepG2 cells","volume":"77","author":"Thabrew","year":"2005","journal-title":"Life Sci."},{"key":"10.1016\/j.phymed.2022.153936_bib0100","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/S0140-6736(16)31012-1","article-title":"Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980\u20132015: a systematic analysis for the Global Burden of Disease Study 2015","volume":"388","author":"Wang","year":"2016","journal-title":"Lancet"},{"key":"10.1016\/j.phymed.2022.153936_bib0101","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13048-015-0177-8","article-title":"Thymoquinone enhances cisplatin-response through direct tumor effects in a syngeneic mouse model of ovarian cancer","volume":"8","author":"Wilson","year":"2015","journal-title":"J. Ovarian Res."},{"key":"10.1016\/j.phymed.2022.153936_bib0102","first-page":"19","article-title":"Thymoquinone down-regulates VEGFA and up-regulates FLT1 transcriptional levels in human breast cancer cells","volume":"20","author":"Yegin","year":"2020","journal-title":"Int. J. Hum. Genet."},{"key":"10.1016\/j.phymed.2022.153936_bib0103","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0378-8741(95)01241-5","article-title":"Traditional medicine in Turkey. V. Folk medicine in the inner Taurus mountains","volume":"46","author":"Ye\u015filada","year":"1995","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.phymed.2022.153936_bib0104","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1158\/1535-7163.MCT-08-0124","article-title":"Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways","volume":"7","author":"Yi","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.phymed.2022.153936_bib0105","first-page":"3358","article-title":"Polysaccharide-based nanomedicines for cancer immunotherapy: a review","volume":"6","author":"Zeng","year":"2021","journal-title":"Bioact. Mater."},{"key":"10.1016\/j.phymed.2022.153936_bib0106","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.jss.2016.03.027","article-title":"Gastroprotective effects of sulforaphane and thymoquinone against acetylsalicylic acid\u2013induced gastric ulcer in rats","volume":"203","author":"Zeren","year":"2016","journal-title":"J. Surg. Res."},{"key":"10.1016\/j.phymed.2022.153936_bib0107","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.3892\/ol.2016.4971","article-title":"Thymoquinone chemosensitizes colon cancer cells through inhibition of NF\u2011\u03baB","volume":"12","author":"Zhang","year":"2016","journal-title":"Oncol. Lett."},{"key":"10.1016\/j.phymed.2022.153936_bib0108","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1111\/cas.13808","article-title":"Thymoquinone inhibits the metastasis of renal cell cancer cells by inducing autophagy via AMPK\/mTOR signaling pathway","volume":"109","author":"Zhang","year":"2018","journal-title":"Cancer Sci."},{"key":"10.1016\/j.phymed.2022.153936_bib0109","article-title":"Synergistic role of thymoquinone on anticancer activity of 5-fluorouracil in triple-negative breast cancer cells","author":"Zheng","year":"2021","journal-title":"Anticancer Agents Med. Chem."},{"key":"10.1016\/j.phymed.2022.153936_bib0110","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2019.152921","article-title":"Ellagic acid synergistically potentiates inhibitory activities of chemotherapeutic agents to human hepatocellular carcinoma","volume":"59","author":"Zhong","year":"2019","journal-title":"Phytomedicine"},{"key":"10.1016\/j.phymed.2022.153936_bib0111","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1097\/CEJ.0b013e32834dbbfd","article-title":"Combination chemoprevention: future direction of colorectal cancer prevention","volume":"21","author":"Zhou","year":"2012","journal-title":"Eur. J. Cancer Prev."},{"key":"10.1016\/j.phymed.2022.153936_bib0112","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.7150\/thno.17736","article-title":"Theranostic DNAzymes","volume":"7","author":"Zhou","year":"2017","journal-title":"Theranostics"}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711322000149?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711322000149?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T04:14:58Z","timestamp":1778559298000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711322000149"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4]]},"references-count":112,"alternative-id":["S0944711322000149"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2022.153936","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2022,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Combinatorial effect of thymoquinone with chemo agents for tumor therapy","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2022.153936","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier GmbH. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"153936"}}