Targeting melanocyte and melanoma stem cells by 8-hydroxy-2-dipropylaminotetralin Journal Article

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Authors: Bonchak, J. G.; Eby, J. M.; Willenborg, K. A.; Chrobak, D.; Henning, S. W.; Krzywiec, A.; Johnson, S. L.; Le Poole, I. C.
Article Title: Targeting melanocyte and melanoma stem cells by 8-hydroxy-2-dipropylaminotetralin
Abstract: Monobenzyl ether of hydroquinone (MBEH) is cytotoxic towards melanocytes. Its treatment efficacy is limited by an inability to eradicate stem cells. By contrast, 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-DPAT) affects melanocyte stem cell survival. MBEH and 8-DPAT were added to melanocytes and melanoma cells to compare cytotoxicity. Stem cell content among viable cells was determined by fluorocytometry using markers CD34, Pax3, and CD271. Immunostaining was used to identify stem cells in skin explants treated with MBEH or 8-DPAT ex vivo. Mice were exposed to MBEH or 8-DPAT and scanned for depigmentation before harvesting skin. MBEH exposure prompted a relative increase in stem cells among cultured melanocytes and melanoma cells, as treatment preferentially eliminated differentiated cells and spared the stem cells. Viability of this remaining, enriched stem cell population was however rapidly reduced by exposure to 8-DPAT within melanocyte and melanoma cell cultures. In human skin explants, the abundance of melanocyte stem cells was also visibly reduced after 8-DPAT treatment, in contrast to tissue exposed to MBEH. Meanwhile, significant depigmentation of the mouse pelage and loss of differentiated melanocytes was observed in vivo in response to topical application of MBEH, but not 8-DPAT. Prolonged application of the latter agent instead appeared to effectively reduce the abundance of melanocyte stem cells in the dermis. This furthers the idea that MBEH and 8-DPAT target complementary cell populations. Results indicate that combination treatment may demonstrate superior therapeutic activity by eliminating both differentiated and tumor initiating populations.
Journal Title: Archives of Biochemistry and Biophysics
Volume: 563
ISSN: 1096-0384; 0003-9861
Publisher: Unknown  
Journal Place: United States
Date Published: 2014
Start Page: 71
End Page: 78
Language: eng
DOI/URL:

10.1016/j.abb.2014.07.033
Notes: LR: 20150401; GR: R01 GM056988/GM/NIGMS NIH HHS/United States; GR: R03 CA128068/CA/NCI NIH HHS/United States; GR: R03 CA128068/CA/NCI NIH HHS/United States; JID: 0372430; 0 (Hydroquinones); 0 (Skin Lightening Preparations); 78950-78-4 (8-Hydroxy-2-(di-n-propylamino)tetralin); 9L2KA76MG5 (monobenzone); NIHMS620110; OID: NLM: NIHMS620110 [Available on 12/01/15]; OID: NLM: PMC4221435 [Available on 12/01/15]; OTO: NOTNLM; PMCR: 2015/12/01 00:00; 2014/03/25 [received]; 2014/07/26 [revised]; 2014/07/29 [accepted]; 2014/08/14 [aheadofprint]; ppublish