{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T20:02:34Z","timestamp":1740168154606,"version":"3.37.3"},"reference-count":25,"publisher":"Georg Thieme Verlag KG","issue":"12","funder":[{"DOI":"10.13039\/501100006662","name":"Ardabil University of Medical Sciences","doi-asserted-by":"crossref","award":["Grant No. 0694"],"award-info":[{"award-number":["Grant No. 0694"]}],"id":[{"id":"10.13039\/501100006662","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Background Malignant melanoma is a common form of skin cancer that contains different cell types recognized by various cell surface markers. Dacarbazine-based combination chemotherapy is frequently used for the treatment of melanoma. Despite its potent anticancer properties, resistance to dacarbazine develops in malignant melanoma. Here, we aim to improve response to dacarbazine therapy by pretreatment with all-trans retinoic acid (ATRA) in CD117+ melanoma cells.<\/jats:p><jats:p>Methods The CD117+ melanoma cells were sorted from A375 malignant melanoma cell line using magnetic-activated cell sorting (MACS). The cell viability was examined by cell proliferation assay (MTT). Apoptosis was determined by acridine orange\/ ethidium bromide staining. Indeed, we performed flow cytometry to evaluate the cell cycle arrest.<\/jats:p><jats:p>Results Here, the CD117+ melanoma cells were incubated with various concentrations of ATRA, dacarbazine, and their combination to determine IC50 values. We found that 20\u2009\u00b5M ATRA treatment followed by dacarbazine was found to be more effective than dacarbazine alone. There was an indication that the combination of ATRA with dacarbazine (ATRA\/dacarbazine) caused more apoptosis and necrosis in the melanoma cells (P&lt;0.05). Furthermore, ATRA\/dacarbazine treatment inhibited the cell at the G0\/G1 phase, while dacarbazine alone inhibited the cells at S phase.<\/jats:p><jats:p>Conclusion Collectively, combined treatment with ATRA and dacarbazine induced more apoptosis and enhanced the cell cycle arrest of CD117+ melanoma cells. These results suggested that ATRA increased the sensitivity of melanoma cells to the effect of dacarbazine.<\/jats:p>","DOI":"10.1055\/a-1240-0072","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T22:49:46Z","timestamp":1602024586000},"page":"563-569","source":"Crossref","is-referenced-by-count":1,"title":["In Vitro Anticancer Effects of All-trans Retinoic Acid in Combination with Dacarbazine against CD117+ Melanoma Cells"],"prefix":"10.1055","volume":"70","author":[{"given":"Bahareh Mohammadi","family":"Jobani","sequence":"additional","affiliation":[{"name":"Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elham","family":"Mohebi","sequence":"additional","affiliation":[{"name":"Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8870-1255","authenticated-orcid":false,"given":"Nowruz","family":"Najafzadeh","sequence":"additional","affiliation":[{"name":"Research Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,10,6]]},"reference":[{"key":"ref1","first-page":"1071","article-title":"Cutaneous melanoma: From pathogenesis to therapy","volume":"52","author":"G C Leonardi","year":"2018","journal-title":"International Journal of Oncology"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"djx030","DOI":"10.1093\/jnci\/djx030","article-title":"Annual report to the nation on the status of cancer, 1975\u20132014, featuring survival","volume":"109","author":"A Jemal","year":"2017","journal-title":"JNCI: Journal of the National Cancer Institute"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"3138","DOI":"10.1038\/sj.onc.1206454","article-title":"Apoptosis and melanoma chemoresistance","volume":"22","author":"M S Soengas","year":"2003","journal-title":"Oncogene"},{"key":"ref5","first-page":"21","article-title":"Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview","volume":"19","author":"L Serrone","year":"2000","journal-title":"Journal of Experimental & Clinical Cancer Research: CR"},{"key":"ref7","first-page":"427","article-title":"Metastatic melanoma: Chemotherapy","volume":"5","author":"E Bajetta","year":"2002","journal-title":"In: Seminars in Oncology"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0145-2126(01)00028-5","article-title":"Classes of c-KIT activating mutations: proposed mechanisms of action and implications for disease classification and therapy","volume":"25","author":"B J Longley","year":"2001","journal-title":"Leukemia Research"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/nature07427","article-title":"Generation of a prostate from a single adult stem cell","volume":"456","author":"K G Leong","year":"2008","journal-title":"Nature"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/S1357-2725(99)00078-3","article-title":"Early signaling pathways activated by c-Kit in hematopoietic cells","volume":"31","author":"D Linnekin","year":"1999","journal-title":"The International Journal of Biochemistry & Cell Biology"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3390\/biomedicines6010031","article-title":"CD117\/c-kit in cancer stem cell-mediated progression and therapeutic resistance","volume":"6","author":"B M Foster","year":"2018","journal-title":"Biomedicines"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"343","DOI":"10.5858\/2006-130-343-UOCIID","article-title":"Utility of CD117 immunoreactivity in differentiating metastatic melanoma from clear cell sarcoma","volume":"130","author":"J J Garcia","year":"2006","journal-title":"Archives of Pathology & Laboratory Medicine"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/carcin\/24.2.185","article-title":"All-trans retinoic acid (atRA) differentially induces apoptosis in matched primary and metastatic melanoma cells\u2013a speculation on damage effect of atRA via mitochondrial dysfunction and cell cycle redistribution","volume":"24","author":"H Zhang","year":"2003","journal-title":"Carcinogenesis"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/imm.12768","article-title":"Topical treatment of all-trans retinoic acid inhibits murine melanoma partly by promoting CD8(+) T-cell immunity","volume":"152","author":"W Yin","year":"2017","journal-title":"Immunology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/j.ejca.2004.04.030","article-title":"Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years?","volume":"40","author":"A M Eggermont","year":"2004","journal-title":"European Journal of Cancer"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.biopha.2015.08.019","article-title":"Low-dose all-trans retinoic acid enhances cytotoxicity of cisplatin and 5-fluorouracil on CD44(+) cancer stem cells","volume":"74","author":"N Najafzadeh","year":"2015","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"ref17","first-page":"2033","article-title":"All-trans retinoic acid enhances cisplatin-induced apoptosis in human ovarian adenocarcinoma and in squamous head and neck cancer cells","volume":"3","author":"S Aebi","year":"1997","journal-title":"Clinical Cancer Research"},{"key":"ref19","first-page":"423","article-title":"Retinoic acid inhibits human melanoma tumor cell invasion","volume":"10","author":"W Wood","year":"1990","journal-title":"Anticancer Research"},{"key":"ref21","first-page":"2477","article-title":"Expression and up-regulation of retinoic acid receptor-\u03b2 is associated with retinoid sensitivity and colony formation in esophageal cancer cell lines","volume":"59","author":"X-C Xu","year":"1999","journal-title":"Cancer Research"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"7305","DOI":"10.1038\/sj.onc.1206936","article-title":"Retinoids in cancer therapy and chemoprevention: promise meets resistance","volume":"22","author":"S J Freemantle","year":"2003","journal-title":"Oncogene"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1634\/theoncologist.1-5-305","article-title":"All-Trans-Retinoic Acid Pharmacology and Its Impact on the Treatment of Acute Promyelocytic Leukemia","volume":"1","author":"P C Adamson","year":"1996","journal-title":"The Oncologist"},{"key":"ref24","first-page":"1","article-title":"Co-delivery of Dacarbazine and All-Trans Retinoic Acid (ATRA) Using Lipid Nanoformulations for Synergistic Antitumor Efficacy Against Malignant Melanoma","volume":"15","author":"C Li","year":"2020","journal-title":"Nanoscale Research Letters"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1002\/pbc.22603","article-title":"Retinoic acid enhances sensitivity of neuroblastoma cells for imatinib mesylate","volume":"55","author":"I Neumann","year":"2010","journal-title":"Pediatric Blood & Cancer"},{"key":"ref26","first-page":"931","article-title":"Synergistic antitumor effects of a combination of interferons and retinoic acid on human tumor cells in vitro and in vivo","volume":"3","author":"D J Lindner","year":"1997","journal-title":"Clinical Cancer Research"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.4161\/cbt.10.11.13556","article-title":"The ubiquitin-proteasome pathway plays essential roles in ATRA-induced leukemia cells G0\/G1 phase arrest and transition into granulocytic differentiation","volume":"10","author":"Y Fang","year":"2010","journal-title":"Cancer Biology & Therapy"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1210\/endo.142.6.8201","article-title":"Redox control of retinoic acid receptor activity: a novel mechanism for retinoic acid resistance in melanoma cells","volume":"142","author":"K Demary","year":"2001","journal-title":"Endocrinology"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"132","DOI":"10.3390\/ijms19010132","article-title":"Why differentiation therapy sometimes fails: molecular mechanisms of resistance to retinoids","volume":"19","author":"P Chlapek","year":"2018","journal-title":"International Journal of Molecular 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