Effects of 1,25-dihydroxyvitamin D3 on proliferation and differentiation of Caco-2 cells

Abstract

The effect of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], or calcitriol, on the proliferation and differentiation of Caco-2 cells was studied. Vitamin D receptor mRNA was detected in both pre- and postconfluent cells, and its abundance was unchanged with time and in response to calcitriol. 1,25-(OH)2D3-binding activity increased during differentiation, but there was no difference in binding between 1,25-(OH)2D3-treated and control cells. 1,25-(OH)2D3 caused a dose-dependent reduction in proliferation, as assessed by [3H]thymidine incorporation and DNA content. 1,25-(OH)2D3 significantly enhanced the normal rise in alkaline phosphatase activity during differentiation and increased alkaline phosphatase mRNA abundance. In contrast, 1,25-(OH)2D3 inhibited the normal rise in sucrase-isomaltase activity and the corresponding mRNA level, although the inhibition occurred after the initial period of cell differentiation (> 10 days postplating). Morphological analysis demonstrated that by day 12 postplating, 1,25-(OH)2D3 increased the mean dome diameter and microvillus length and density. Although 1,25-(OH)2D3 decreases the proliferation of Caco-2 cells and enhances certain parameters of differentiation, not all brush-border hydrolases respond in a similar fashion, making it necessary to interpret with caution their individual use as markers of differentiation.

Control of TCF-4 Expression by VDR and Vitamin D in the Mouse Mammary Gland and Colorectal Cancer Cell Lines

“…Although all of these cells increased expression of TCF4 in response to vitamin D we chose to use the human colorectal adenocarcinoma cell line, CaCo2 for several reasons. These cells are well-studied in the context of vitamin D signaling and their growth is inhibited by 1,25(OH) 2 D 3 [27]. Furthermore, they are a unique system that mimics normal gut epithelium as once they become confluent they differentiate in culture [28].…”

Expression of Enzymatically Active CYP3A4 by Caco-2 Cells Grown on Extracellular Matrix-Coated Permeable Supports in the Presence of 1α,25-Dihydroxyvitamin D3

“…These measurements are similar to those obtained by Wilson et al(17.2 and 0.94 m), who used uncoated nitrocellulose filters(12), but less than those obtained byHidalgo et al (29.6 and 1.19 m), who used collagen type I-coated polycarbonate filters(11). The microvillar height was also less than that reported by Halline et al(1.52 m)for Caco-2 cells grown on plastic and treated with 0.1 M 1␣,25-(OH) 2 -D 3 in medium containing 20% FBS(48). A representative Caco-2 cell grown on a Matrigel-coated polycarbonate membrane and treated with 1␣,25-(OH) 2 -D 3 is shown in…”

The Intestinal Absorption of Folates

“…Similarly, as Caco-2 cells became confluent and differentiated, expression of both transporters increased (122). Although vitamin D 3 promotes differentiation (124, 125), it is uncertain whether the increase in PCFT expression that occurs with the differentiation of Caco-2 cells, or in the villus tip versus crypt cells, is related specifically to vitamin D 3 regulation.…”