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Zinc Inhibits Cadherin 1 Expression Induced by 1α,25-Dihydroxyvitamin D₃ in Colon Cancer Cells.

By: Michiyasu Ishizawa, Ayako Hirayu, Makoto Makishima

Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, Japan.
2021-09-06; doi: 10.21873/anticanres.15357

Abstract

Background

Zinc is a mineral that is essential for biological molecules, such as transcription factors, and is involved in the maintenance of intestinal homeostasis. Vitamin D signaling is mediated by vitamin D receptor (VDR) activated by 1α,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] and is also important in intestinal functions, such as calcium absorption and epithelial barrier maintenance. However, the crosstalk between vitamin D signaling and zinc signaling in intestinal cells remains poorly understood.

Materials

Colon cancer SW480 and HCT116 cells were treated with zinc chloride (ZnCl₂) with/without 1,25(OH)₂D₃ Expression of zinc-inducible genes [metallothionein 1A (MT1A) and MT2A] and VDR target genes [cytochrome P450 family 24 subfamily A member 1 (CYP24A1), transient receptor potential cation channel subfamily V member 6 (TRPV6) and cadherin 1 (CDH1)] was examined.

Results

Treatment of cells with ZnCl₂ effectively induced MT1A and MT2A mRNA expression, and interestingly suppressed mRNA expression of CDH1, which was induced by 1,25(OH)₂D₃ in both cell lines. ZnCl₂ also reduced the CDH1 protein level in HCT116 cells.

Conclusion

Zinc signaling suppresses VDR-induced expression of CDH1.