Kh. Cho et al., CALCIPOTRIOL (MC-903), A SYNTHETIC DERIVATIVE OF VITAMIN-D-3 STIMULATES DIFFERENTIATION OF SQUAMOUS CARCINOMA CELL-LINE IN THE RAFT CULTURE, Anticancer research, 16(1), 1996, pp. 337-347
We investigated whether calcipotriol, a synthetic derivative of vitami
n D-3 has the ability to correct defects in the control of proliferati
on and differentiation of human squamous carcinoma cells using the raf
t culture of SCC 13 cell line. Calcipotriol treatment at concentration
s of 10(-8)-10(-6) M considerably enhanced terminal differentiation of
SCC 13 cells, as shown by the appearance of enucleated-eosinophilic c
ells as well as granular cells in their upper cell layers. Immunohisto
chemical staining showed marked increased in the differentiation of ma
rker proteins such as keratin 1, involucrin, or filaggrin expressing c
ells in their upper layers. The elevated expression at protein level w
as confirmed by immunoblotting analysis. Furthermore, calcipotriol als
o stimulated basal cell marker proteins such as keratin 14 and EGF rec
eptor. However, the numbers of basal marker expressing cells within th
e architecture of SCC 13 raft culture were markedly reduced upon calci
potriol treatment, and their localization was mainly restricted in the
innermost cell layer. In addition, calcipotriol stimulated EGF recept
or biosynthesis for the first 16 hours post treatment and subsequently
inhibited [H-3]-thymidine incorporation of SCC 13 cells at 24 hours.
In this study, we have clearly demonstrated that the long term applica
tion of calcipotriol considerably improves the complex defects in the
regulation of proliferation.