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1,25-Dihydroxyvitamin D-3 enhances NK susceptibility of human melanoma cells via Hsp60-mediated FAS expression

Authors
Lee, Ji H.Park, SunyoungCheon, SoyoungLee, Joo H.Kim, SunghanHur, Dae Y.Kim, Tae S.Yoon, Suk R.Yang, YoolheeBang, Sa I.Park, HyunjeongLee, Hoon T.Cho, Daeho
Issue Date
Oct-2011
Publisher
WILEY-BLACKWELL
Keywords
1 alpha,25(OH)(2)D-3; Fas; HSP; Melanoma; NK cells
Citation
EUROPEAN JOURNAL OF IMMUNOLOGY, v.41, no.10, pp 2937 - 2946
Pages
10
Journal Title
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume
41
Number
10
Start Page
2937
End Page
2946
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/12483
DOI
10.1002/eji.201141597
ISSN
0014-2980
1521-4141
Abstract
The active metabolite of vitamin D-3, 1 alpha,25(OH)(2)D-3, displays anticancer effects by regulating cell cycle and apoptosis in many cancer cells. However, it has not been determined whether 1 alpha,25(OH)(2)D-3 increases the susceptibility of cancer cells to NK cells. Here, we investigated the anticancer effect of 1 alpha,25(OH)(2)D-3 in human melanoma cell lines by investigating enhancement of NK susceptibility and elucidating the mediator of NK cytotoxicity. 1 alpha,25(OH)(2)D-3-resistant melanoma cells (G-361 and SK-MEL-5) treated with 1 alpha,25(OH)(2)D-3 showed higher susceptibility to NK cells with up-regulation of Fas expression. Furthermore, G-361 cells treated with 1 alpha,25(OH)(2)D-3 showed significantly increased caspase activity. In addition to Fas up-regulation, expression of heat shock protein 60 (Hsp60) was elevated by 1 alpha,25(OH)(2)D-3. Increased expression of Hsp60 by 1 alpha,25(OH)(2)D-3 was related to not only up-regulation of Fas expression but also to NK susceptibility of G-361 cells. Taken together, our data suggest that 1 alpha,25(OH)(2)D-3 acts as an anticancer agent by increasing expression of Fas on the surface of melanoma cells through Hsp60 induction and strengthens caspase sensitivity to Fas-mediated apoptotic pathway by NK cells. 1 alpha,25(OH)(2)D-3 treatment may therefore have a preventive role in melanoma occurrence or potentiate the anticancer effects of NK-cell immune therapy.
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