Mechanism of antimitogenic action of vitamin D in human colon carcinoma cells: Relevance for suppression of epidermal growth factor-stimulated cell growth
Wm. Tong et al., Mechanism of antimitogenic action of vitamin D in human colon carcinoma cells: Relevance for suppression of epidermal growth factor-stimulated cell growth, ONCOL RES, 11(2), 1999, pp. 77-84
Because the efficacy of 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25-(OH)(2)
D-3] in treatment of colon cancer might critically depend on its ability to
specifically counteract epidermal growth factor (EGF)-stimulated tumor cel
l growth, we utilized human colon adenocarcinoma-derived cells in primary c
ulture as well as the Caco-2 cell line to elucidate possible sites of inter
action of 1 alpha,25-(OH)(2)D-3 with signaling from EGF receptor activation
. In both types of colon cancer cells investigated, 10(-8) M 1 alpha,25-(OH
)(2)D-3 reduced basal cell proliferation by about 50%, and prevented any ri
se in proliferation when colon cancer cells were treated with 25 ng/ml EGF:
this can be explained by a marked inhibitory effect of 1 alpha,25-(OH)(2)D
-3 on EGFR mRNA and protein expression. The steroid hormone also seemingly
promotes EGF-induced internalization of apical and basolateral membrane EGF
R. In addition, 1 alpha,25-(OH)(2)D-3 significantly reduced basal and EGF-s
timulated expression of cyclin D1 at the mRNA and protein level in primary
cultures as well as in the Caco-2 cell line. The ability of 1 alpha,25(OH)(
2)D-3 to interfere with a key event in cell cycle control and thereby to bl
ock mitogenic signaling from EGF could be seen as advantageous for the pote
ntial use of vitamin D compounds in colon cancer therapy.