{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:57:55Z","timestamp":1783699075720,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T00:00:00Z","timestamp":1492992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010180","name":"Emporia State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010180","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20 GM103418"],"award-info":[{"award-number":["P20 GM103418"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec><jats:label\/><jats:p>Vitamin C has been used in complementary and alternative medicine for cancers regardless of its ineffectiveness in clinical trials and the paradoxical effects antioxidants have on cancer. Vitamin C was found to induce cytotoxicity against cancers. However, the mechanisms of action have not been fully elucidated, and the effects of vitamin C on human malignant melanoma have not been examined. This study revealed that vitamin C at millimolar concentrations significantly reduced the cell viability as well as invasiveness, and induced apoptosis in human malignant melanoma cells. Vitamin C displayed stronger cytotoxicity against the Vemurafenib\u2010resistance cell line A2058 compared with SK\u2010MEL\u201028. In contrast, vitamin C at micromolar concentrations promoted cell growth, migration and cell cycle progression, and protected against mitochondrial stress. Vemurafenib paradoxically activated the RAS\u2010RAF\u2010MEK\u2010ERK signaling pathway in the Vemurafenib\u2010resistant A2058, however, vitamin C abolished the activations. Vitamin C displayed synergistic cytotoxicity with Vemurafenib against the Vemurafenib\u2010resistant A2058. In vivo assay suggested that lower dosage (equivalent to 0.5\u2009g\/70\u2009kg) of vitamin C administered orally increased the melanoma growth. Therefore, vitamin C may exert pro\u2010 or anti\u2010melanoma effect depending on concentration. The combination of vitamin C at high dosage and Vemurafenib is promising in overcoming the action of drug resistance.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22654","type":"journal-article","created":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T01:21:12Z","timestamp":1490923272000},"page":"1965-1976","source":"Crossref","is-referenced-by-count":45,"title":["Vitamin C at high concentrations induces cytotoxicity in malignant melanoma but promotes tumor growth at low concentrations"],"prefix":"10.1002","volume":"56","author":[{"given":"Guang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Emporia State University Emporia Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Emporia State University Emporia Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7997-3849","authenticated-orcid":false,"given":"Yixin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Emporia State University Emporia Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21254"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/ced.12015"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05661"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-8-39"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09454"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103782"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2001.10719184"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007653"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad3740"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635589609514458"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804226105"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-10-1072"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.02.016"},{"key":"e_1_2_8_15_1","first-page":"249","article-title":"Pharmacological ascorbic acid suppresses syngeneic tumor growth and metastases in hormone\u2010refractory prostate cancer","volume":"24","author":"Pollard HB","year":"2010","journal-title":"In Vivo"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1713"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506390102"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702854104"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007154"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-016-5271-z"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(85)90154-5"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.73.10.3685"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.9.4538"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197909273011303"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-140-7-200404060-00010"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21336"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.08.057"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12197"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0097276"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10868"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.22654","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.22654","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mc.22654","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.22654","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T15:40:27Z","timestamp":1694187627000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.22654"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,24]]},"references-count":29,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["10.1002\/mc.22654"],"URL":"https:\/\/doi.org\/10.1002\/mc.22654","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,24]]}}}