Antiproliferative Activity of Non-Calcemic Vitamin D Analogs on Human Melanoma Lines in Relation to VDR and PDIA3 Receptors.

Vitamin D is a precursor for secosteroidal hormones, which demonstrate pleiotropic biological activities, including the regulation of growth and the differentiation of normal and malignant cells. Our previous studies have indicated that the inhibition of melanoma proliferation by a short side-chain, low calcemic analog of vitamin D-21(OH)pD is not fully dependent on the expression of vitamin D receptor (VDR). We have examined the effects of classic vitamin D metabolites, 1,25(OH)₂D₃ and 25(OH)D₃, and two low calcemic vitamin D analogs, (21(OH)pD and calcipotriol), on proliferation, mRNA expression and vitamin D receptor (VDR) translocation in three human melanoma cell lines: WM98, A375 and SK-MEL-188b (subline b of SK-MEL-188, which lost responsiveness to 1,25(OH)₂D₃ and became VDRCYP27B1).

Antitumor effects of vitamin D analogs on hamster and mouse melanoma cell lines in relation to melanin pigmentation.

Deregulated melanogenesis is involved in melanomagenesis and melanoma progression and resistance to therapy. Vitamin D analogs have anti-melanoma activity. While the hypercalcaemic effect of the active form of Vitamin D (1,25(OH)2D3) limits its therapeutic use, novel Vitamin D analogs with a modified side chain demonstrate low calcaemic activity.

Geldanamycin-induced osteosarcoma cell death is associated with hyperacetylation and loss of mitochondrial pool of heat shock protein 60 (hsp60).

Osteosarcoma is one of the most malignant tumors of childhood and adolescence that is often resistant to standard chemo- and radio-therapy. Geldanamycin and geldanamycin analogs have been recently studied as potential anticancer agents for osteosarcoma treatment. Here, for the first time, we have presented novel anticancer mechanisms of geldanamycin biological activity.

KU812 basophils express urocortin, CRH-R, MC1R and steroidogenic enzymes and secrete progesterone.

Little is known about neuroendocrine regulation of human basophils by components of the hypothalamic-pituitary-adrenal (HPA) axis. Using the basophil cell line KU812 as an in vitro model, we show that these cells express urocortin 1-3, specific isoforms of the corticotropin-releasing hormone (CRH) receptor (CRH-R)1 and CRH-R2 but not CRH itself. The precursor for melanocortins and β-endorphin, proopiomelanocortin, was not detectable, while the melanocortin-1 receptor was present at RNA and protein level in KU812 cells.