PMC

Effect of vitamin D3 on TXNIP mRNA and protein in liver cancer cell lines. (a) mRNA expression; Huh7 and HepG2 cells treated with 10 nM vitamin D3 for 24 h, Hep3B cells treated with 100 nM vitamin D3 for 48 h (*P < 0.001, **P < 0.05, ***P < 0.01). (b) Protein and relative densitometry; Hep3B cells treated with 10 nM vitamin D3 for 72 h (*P < 0.005). GAPDH, glyceraldehyde 3-phosphate dehydrogenase.

Effect of vitamin D3 on CDKN1A mRNA expression in liver cancer cells. (a) HepG2 cells treated with 10 nM vitamin D3 for 24 h (*P < 0.001). (b) Hep3B cells treated with 100 nM vitamin D3 for 48 h (**P < 0.0005). GAPDH, glyceraldehyde 3-phosphate dehydrogenase.

Vitamin D3 inhibits liver cancer cell proliferation. (A) Hep3B and HepG2 cells were treated with vitamin D3 for 24, 48 or 72 h prior to the MTT assay. (B) Annexin V assay of the effects 1,200 nM vitamin D3 on the apoptosis of Hep3B and HepG2 cells determined by flow cytometry. (C) miR-15a-5p, miR-203a-3p and miR-214-3p expression assayed by reverse transcription-quantitative PCR. *P<0.05 and **P<0.01 vs. mimics-ctrl. miR, microRNA.

Positive effects of vitamin D₃ in the allo-HSCT setting. Vitamin D₃ affects a broad variety of cells of the adaptive and innate immune system which play an important role in boosting GvL responses while alleviating GvHD. On side of GvHD, proliferation of T cells is inhibited and anti-inflammatory differentiation is favored. Vitamin D₃ enhances autophagy, phagocytic activity and tolerogenic capacity of macrophages. Vitamin D₃-dependent release of antimicrobial peptides by macrophages fortifies GvI effects, increases cell integrity, and induces cell death of bacteria. DCs are inhibited in proliferation and reduce Th1 and Th17 responses while the T_reg population increases. Vitamin D₃ triggers apoptosis and cell cycle arrest of B cells and inhibits antibody secretion. Vitamin D₃ reduces cytotoxic activity of NK cells and impedes neutrophils to secrete pro-inflammatory cytokines. In case of GvL, apoptosis, autophagy and differentiation of cancer cells are directly enhanced by vitamin D₃, whereas inflammation and angiogenesis are reduced. Vitamin D₃ enhances ADCC and ADCP of cancer cells by macrophages directly or by release of LL-37.