Abstract
The active metabolite of vitamin D 3, 1α,25(OH) 2D 3, displays anticancer effects by regulating cell cycle and apoptosis in many cancer cells. However, it has not been determined whether 1α,25(OH) 2D 3 increases the susceptibility of cancer cells to NK cells. Here, we investigated the anticancer effect of 1α,25(OH) 2D 3 in human melanoma cell lines by investigating enhancement of NK susceptibility and elucidating the mediator of NK cytotoxicity. 1α,25(OH) 2D 3-resistant melanoma cells (G-361 and SK-MEL-5) treated with 1α,25(OH) 2D 3 showed higher susceptibility to NK cells with up-regulation of Fas expression. Furthermore, G-361 cells treated with 1α,25(OH) 2D 3 showed significantly increased caspase activity. In addition to Fas up-regulation, expression of heat shock protein 60 (Hsp60) was elevated by 1α,25(OH) 2D 3. Increased expression of Hsp60 by 1α,25(OH) 2D 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 1α,25(OH) 2D 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. 1α,25(OH) 2D 3 treatment may therefore have a preventive role in melanoma occurrence or potentiate the anticancer effects of NK-cell immune therapy.
Original language | English |
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Pages (from-to) | 2937-2946 |
Number of pages | 10 |
Journal | European Journal of Immunology |
Volume | 41 |
Issue number | 10 |
DOIs | |
Publication status | Published - 2011 Oct |
Keywords
- 1α,25(OH) D
- Fas
- HSP
- Melanoma
- NK cells
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology