{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T07:57:38Z","timestamp":1782633458967,"version":"3.54.5"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"name":"Deputy of Research and Technology","award":["1881"],"award-info":[{"award-number":["1881"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Med Oncol"],"DOI":"10.1007\/s12032-022-01863-0","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T19:02:37Z","timestamp":1665601357000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["5-FU and the dietary flavonoid carvacrol: a synergistic combination that induces apoptosis in MCF-7 breast cancer cells"],"prefix":"10.1007","volume":"39","author":[{"given":"Saleh","family":"Azimi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamed","family":"Esmaeil Lashgarian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vajihe","family":"Ghorbanzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayat","family":"Moradipour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lale","family":"Pirzeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2477-9461","authenticated-orcid":false,"given":"Hassan","family":"Dariushnejad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"issue":"3","key":"1863_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2021;71(3):209\u201349.","journal-title":"Cancer J Clin"},{"key":"1863_CR2","doi-asserted-by":"publisher","first-page":"112375","DOI":"10.1016\/j.biopha.2021.112375","volume":"145","author":"JA Malik","year":"2022","unstructured":"Malik JA, Ahmed S, Jan B, Bender O, Al Hagbani T, Alqarni A, Anwar S. Drugs repurposed: an advanced step towards the treatment of breast cancer and associated challenges. Biomed Pharmacother. 2022;145:112375.","journal-title":"Biomed Pharmacother"},{"issue":"6","key":"1863_CR3","first-page":"2526","volume":"12","author":"M Pa\u0161kevi\u010di\u016bt\u0117","year":"2022","unstructured":"Pa\u0161kevi\u010di\u016bt\u0117 M, Petrikait\u0117 V. Effect of natural flavonoids to reverse P-glycoprotein-related multidrug resistance in breast cancer cell cultures. Am J Cancer Res. 2022;12(6):2526.","journal-title":"Am J Cancer Res"},{"key":"1863_CR4","doi-asserted-by":"crossref","unstructured":"Mawalizadeh F, Mohammadzadeh G: Quercetin Potentiates the Chemosensitivity of Human Breast Cancer Cells to 5-Fluorouracil. 2021.","DOI":"10.21203\/rs.3.rs-682735\/v1"},{"key":"1863_CR5","doi-asserted-by":"publisher","first-page":"112599","DOI":"10.1016\/j.biopha.2021.112599","volume":"146","author":"NH Shehatta","year":"2022","unstructured":"Shehatta NH, Okda TM, Omran GA, Abd-Alhaseeb MM. Baicalin; a promising chemopreventive agent, enhances the antitumor effect of 5-FU against breast cancer and inhibits tumor growth and angiogenesis in Ehrlich solid tumor. Biomed Pharmacother. 2022;146:112599.","journal-title":"Biomed Pharmacother"},{"key":"1863_CR6","doi-asserted-by":"publisher","first-page":"102107","DOI":"10.1016\/j.jddst.2020.102107","volume":"61","author":"S Amirsaadat","year":"2021","unstructured":"Amirsaadat S, Jafari-Gharabaghlou D, Alijani S, Mousazadeh H, Dadashpour M, Zarghami N. Metformin and Silibinin co-loaded PLGA-PEG nanoparticles for effective combination therapy against human breast cancer cells. J Drug Deliv Sci Technol. 2021;61:102107.","journal-title":"J Drug Deliv Sci Technol"},{"key":"1863_CR7","doi-asserted-by":"publisher","first-page":"102318","DOI":"10.1016\/j.jddst.2020.102318","volume":"61","author":"S Samadzadeh","year":"2021","unstructured":"Samadzadeh S, Mousazadeh H, Ghareghomi S, Dadashpour M, Babazadeh M, Zarghami N. In vitro anticancer efficacy of Metformin-loaded PLGA nanofibers towards the post-surgical therapy of lung cancer. J Drug Deliv Sci Technol. 2021;61:102318.","journal-title":"J Drug Deliv Sci Technol"},{"issue":"1","key":"1863_CR8","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1515\/chem-2020-0011","volume":"18","author":"T Baj","year":"2020","unstructured":"Baj T, Biernasiuk A, Wr\u00f3bel R, Malm A. Chemical composition and in vitro activity of Origanum vulgare L., Satureja hortensis L., Thymus serpyllum L. and Thymus vulgaris L. essential oils towards oral isolates of Candida albicans and Candida glabrata. Open Chem. 2020;18(1):108\u201318.","journal-title":"Open Chem"},{"issue":"9","key":"1863_CR9","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1002\/ptr.6103","volume":"32","author":"M Sharifi-Rad","year":"2018","unstructured":"Sharifi-Rad M, Varoni EM, Iriti M, Martorell M, Setzer WN, del Mar CM, Salehi B, Soltani-Nejad A, Rajabi S, Tajbakhsh M. Carvacrol and human health: a comprehensive review. Phytother Res. 2018;32(9):1675\u201387.","journal-title":"Phytother Res"},{"issue":"5","key":"1863_CR10","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1182\/blood.V26.5.642.642","volume":"26","author":"E Frei III","year":"1965","unstructured":"Frei III E, Karon M, Levin RH, FREIREICH EJ, Taylor RJ, Hananian J, Selawry O, Holland JF, Hoogstraten B, Wolman IJ. The effectiveness of combinations of antileukemic agents in inducing and maintaining remission in children with acute leukemia. Blood. 1965;26(5):642\u201356.","journal-title":"Blood"},{"issue":"2","key":"1863_CR11","first-page":"185","volume":"4","author":"H Dariushnejad","year":"2014","unstructured":"Dariushnejad H, Zarghami N, Rahmati M, Ghasemali S, Sadeghi Z, Davoodi Z, Tekab HJ, Ghalhar MG. ABT-737, synergistically enhances daunorubicin-mediated apoptosis in acute myeloid leukemia cell lines. Adv Pharm Bulletin. 2014;4(2):185.","journal-title":"Adv Pharm Bulletin"},{"issue":"1","key":"1863_CR12","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/BF02988570","volume":"8","author":"F Ries","year":"1991","unstructured":"Ries F, Dicato M. Treatment of advanced and refractory breast cancer with doxorubicin, vincristine and continuous infusion of verapamil. A phase I-II clinical trial. Med Oncol Tumor Pharmacother. 1991;8(1):39\u201343.","journal-title":"Med Oncol Tumor Pharmacother"},{"issue":"2","key":"1863_CR13","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.tips.2004.12.002","volume":"26","author":"MV Blagosklonny","year":"2005","unstructured":"Blagosklonny MV. Overcoming limitations of natural anticancer drugs by combining with artificial agents. Trends Pharmacol Sci. 2005;26(2):77\u201381.","journal-title":"Trends Pharmacol Sci"},{"issue":"23","key":"1863_CR14","doi-asserted-by":"publisher","first-page":"38022","DOI":"10.18632\/oncotarget.16723","volume":"8","author":"RB Mokhtari","year":"2017","unstructured":"Mokhtari RB, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, Yeger H. Combination therapy in combating cancer. Oncotarget. 2017;8(23):38022.","journal-title":"Oncotarget"},{"issue":"04","key":"1863_CR15","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1055\/a-1766-5491","volume":"72","author":"V Ghorbanzadeh","year":"2022","unstructured":"Ghorbanzadeh V, Aljaf KAH, Wasman HM, Pirzeh L, Azimi S, Dariushnejad H. Carvacrol enhance apoptotic effect of 5-FU on MCF-7 cell line via inhibiting P-glycoprotein: an In-silco and In-vitro study. Drug Res. 2022;72(04):203\u20138.","journal-title":"Drug Res"},{"issue":"2","key":"1863_CR16","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","volume":"70","author":"T-C Chou","year":"2010","unstructured":"Chou T-C. Drug combination studies and their synergy quantification using the Chou-Talalay methodsynergy quantification method. Can Res. 2010;70(2):440\u20136.","journal-title":"Can Res"},{"key":"1863_CR17","doi-asserted-by":"publisher","first-page":"102256","DOI":"10.1016\/j.jddst.2020.102256","volume":"61","author":"E Adlravan","year":"2021","unstructured":"Adlravan E, Nejati K, Karimi MA, Mousazadeh H, Abbasi A, Dadashpour M. Potential activity of free and PLGA\/PEG nanoencapsulated nasturtium officinale extract in inducing cytotoxicity and apoptosis in human lung carcinoma A549 cells. J Drug Deliv Sci Technol. 2021;61:102256.","journal-title":"J Drug Deliv Sci Technol"},{"issue":"3","key":"1863_CR18","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1007\/s10549-014-3105-5","volume":"147","author":"C Vulsteke","year":"2014","unstructured":"Vulsteke C, Pfeil AM, Schwenkglenks M, Pettengell R, Szucs TD, Lambrechts D, Peeters M, van Dam P, Dieudonn\u00e9 A-S, Hatse S. Impact of genetic variability and treatment-related factors on outcome in early breast cancer patients receiving (neo-) adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide, and docetaxel. Breast Cancer Res Treat. 2014;147(3):557\u201370.","journal-title":"Breast Cancer Res Treat"},{"issue":"2","key":"1863_CR19","doi-asserted-by":"publisher","first-page":"e505","DOI":"10.1038\/cddis.2013.26","volume":"4","author":"B Vinod","year":"2013","unstructured":"Vinod B, Antony J, Nair H, Puliyappadamba V, Saikia M, Shyam Narayanan S, Bevin A, John Anto R. Mechanistic evaluation of the signaling events regulating curcumin-mediated chemosensitization of breast cancer cells to 5-fluorouracil. Cell Death Dis. 2013;4(2):e505\u2013e505.","journal-title":"Cell Death Dis"},{"issue":"7","key":"1863_CR20","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1080\/01635581.2019.1599968","volume":"71","author":"N Javan","year":"2019","unstructured":"Javan N, Khadem Ansari MH, Dadashpour M, Khojastehfard M, Bastami M, Rahmati-Yamchi M, Zarghami N. Synergistic antiproliferative effects of co-nanoencapsulated curcumin and chrysin on mda-mb-231 breast cancer cells through upregulating mir-132 and mir-502c. Nutr Cancer. 2019;71(7):1201\u201313.","journal-title":"Nutr Cancer"},{"issue":"12","key":"1863_CR21","doi-asserted-by":"publisher","first-page":"2033","DOI":"10.1016\/j.fct.2006.07.003","volume":"44","author":"N Yoshida","year":"2006","unstructured":"Yoshida N, Koizumi M, Adachi I, Kawakami J. Inhibition of P-glycoprotein-mediated transport by terpenoids contained in herbal medicines and natural products. Food Chem Toxicol. 2006;44(12):2033\u20139.","journal-title":"Food Chem Toxicol"},{"issue":"2","key":"1863_CR22","doi-asserted-by":"publisher","first-page":"353","DOI":"10.3897\/pharmacia.68.e65878","volume":"68","author":"HM Bayoumi","year":"2021","unstructured":"Bayoumi HM, Alkhatib MH, Al-Seeni MN. Carvacrol effect on topotecan cytotoxicity in various human cancer cells in vitro. Pharmacia. 2021;68(2):353\u201363.","journal-title":"Pharmacia"},{"key":"1863_CR23","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.4.1288.bloodjournal8241288","author":"DD Ross","year":"1993","unstructured":"Ross DD, Wooten PJ, Sridhara R, Ordonez JV, Lee EJ, Schiffer CA. Enhancement of daunorubicin accumulation, retention, and cytotoxicity by verapamil or cyclosporin A in blast cells from patients with previously untreated acute myeloid leukemia. Blood. 1993. https:\/\/doi.org\/10.1182\/blood.V82.4.1288.bloodjournal8241288.","journal-title":"Blood"},{"issue":"2","key":"1863_CR24","doi-asserted-by":"publisher","first-page":"e13899","DOI":"10.1111\/and.13899","volume":"53","author":"G Arkali","year":"2021","unstructured":"Arkali G, Aksakal M, Kaya \u015e\u00d6. Protective effects of carvacrol against diabetes-induced reproductive damage in male rats: modulation of Nrf2\/HO-1 signalling pathway and inhibition of Nf-kB-mediated testicular apoptosis and inflammation. Andrologia. 2021;53(2):e13899.","journal-title":"Andrologia"},{"key":"1863_CR25","doi-asserted-by":"publisher","first-page":"105743","DOI":"10.1016\/j.intimp.2019.105743","volume":"75","author":"N Somensi","year":"2019","unstructured":"Somensi N, Rabelo TK, Guimaraes AG, Quintans-Junior LJ, de Souza Ara\u00fajo AA, Moreira JCF, Gelain DP. Carvacrol suppresses LPS-induced pro-inflammatory activation in RAW 2647 macrophages through ERK1\/2 and NF-kB pathway. Intern Immunopharmacol. 2019;75:105743.","journal-title":"Intern Immunopharmacol"}],"container-title":["Medical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-022-01863-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12032-022-01863-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-022-01863-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T20:36:28Z","timestamp":1667334988000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12032-022-01863-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,12]]},"references-count":25,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["1863"],"URL":"https:\/\/doi.org\/10.1007\/s12032-022-01863-0","relation":{},"ISSN":["1559-131X"],"issn-type":[{"value":"1559-131X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,12]]},"assertion":[{"value":"22 August 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 October 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have not disclosed any competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"253"}}