scholarly journals Activation of vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor (PPAR)-signaling pathways through 1,25(OH)2D3in melanoma cell lines and other skin-derived cell lines

2009 ◽  
Vol 1 (4) ◽  
pp. 232-238 ◽  
Author(s):  
Pit Sertznig ◽  
Markus Seifert ◽  
Wolfgang Tilgen ◽  
Jörg Reichrath
Keyword(s):  
Vitamin D ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Vitamin D Receptor ◽  
Melanoma Cell ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Signaling ◽  
Melanoma Cell Lines

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

2018 ◽  
Vol 19 (9) ◽  
pp. 2583 ◽  
Author(s):  
Tomasz Wasiewicz ◽  
Anna Piotrowska ◽  
Justyna Wierzbicka ◽  
Andrzej Slominski ◽  
Michal Zmijewski
Keyword(s):  
Vitamin D ◽  
Cell Lines ◽  
Vitamin D Receptor ◽  
Melanoma Cell ◽  
Human Melanoma ◽  
Side Chain ◽  
Short Side ◽  
Vitamin D Analogs ◽  
Splicing Variants ◽  
Melanoma Cell Lines

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 VDR−/−CYP27B1−/−). All tested compounds efficiently inhibited the proliferation of WM98 and A375 melanoma cells except SK-MEL-188b, in which only the short side-chain vitamin D analog—21(OH)pD was effective. Overall, 21(OH)pD was the most potent compound in all three melanoma cell lines in the study. The lack of responsiveness of SK-MEL-188b to 1,25(OH)2D3, 25(OH)D3 and calcipotriol is explained by a lack of characteristic transcripts for the VDR, its splicing variants as well as for vitamin D-activating enzyme CYP27B1. On the other hand, the expression of VDR and its splicing variants and other vitamin D related genes (RXR, PDIA3, CYP3A4, CYP2R1, CYP27B1, CYP24A1 and CYP11A1) was detected in WM98 and A375 melanomas with the transcript levels being modulated by vitamin D analogs. The expression of VDR isoforms in WM98 cells was stimulated strongly by calcipotriol. The antiproliferative activities of 21(OH)pD appear not to require VDR translocation to the nucleus, which explains the high efficacy of this noncalcemic pregnacalciferol analog in SK-MEL-188b melanoma, that is, VDR−/−. Therefore, we propose that 21(OH)pD is a good candidate for melanoma therapy, although the mechanism of its action remains to be defined.

Vitamin D Receptor and Growth Inhibition by 1,25-Dihydroxyvitamin D3in Human Malignant Melanoma Cell Lines

1996 ◽  
Vol 61 (1) ◽  
pp. 127-133 ◽  
Author(s):  
Stephen R.T. Evans ◽  
A.McGarry Houghton ◽  
Lisa Schumaker ◽  
Richard V. Brenner ◽  
Robert R. Buras ◽  
...  
Keyword(s):  
Vitamin D ◽  
Malignant Melanoma ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Vitamin D Receptor ◽  
Melanoma Cell ◽  
Human Malignant Melanoma ◽  
Malignant Melanoma Cell ◽  
Melanoma Cell Lines

Inhibition of peroxisome proliferator-activated receptor α signaling by vitamin D receptor

2003 ◽  
Vol 312 (2) ◽  
pp. 513-519 ◽  
Author(s):  
Takahiro Sakuma ◽  
Takahide Miyamoto ◽  
Wei Jiang ◽  
Tomoko Kakizawa ◽  
Shin-ich Nishio ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals DNA repair-based classification of melanoma cell lines reveals an effect of mutations in BRAF and NRAS driver genes on DNA repair capacity

2020 ◽  
Author(s):  
Sylvie Sauvaigo ◽  
Manel Benkhiat ◽  
Florian Braisaz ◽  
Julien Girard ◽  
Sarah Libert ◽  
...  
Keyword(s):  
Dna Repair ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Excision Repair ◽  
Mapk Pathway ◽  
Repair Capacity ◽  
Signaling Mechanism ◽  
Dna Repair Capacity ◽  
Melanoma Cell Lines

AbstractMelanoma, the most serious form of skin cancer, frequently involves the dysregulation of key signaling pathways. Treatment strategies presently target the MAPK/ERK pathway, which is overactive in melanomas due in part to BRAF and NRAS mutations, and involve inhibitors against mutated BRAF (vemurafenib or dabrafenib) or MEK kinases (cobimetinib or trametinib), or a combination of the two. Using an established biochip technology, we assessed base excision repair (BER) and nucleotide excision repair (NER) activities in a collection of BRAF mutated (A-375, Colo 829, HT-144, Malme-3M, SK-mel5, SK-mel24 and SK-mel28) and NRAS mutated (M18, MZ2 and SK-mel2) melanoma cell lines, as well as wild-type controls (A7, CHL-1). We evaluated both basal activities (i.e., without treatment) and repair capacities after treatment with vemurafenib or cobimetinib alone, or in combination. Our results indicate that globally the DNA repair capacity of the cell lines was determined by the mutation status of the BRAF and NRAS genes, indicating that the MAPK pathway participates in the regulation of both BER and NER. Treatment of BRAF mutated melanoma cells with vemurafenib alone or the vemurafenib/cobimetinib combination, but not cobimetinib alone, led to reduced DNA repair capacity in about 60% of the BRAF mutated samples, indicating that signaling pathway inhibition can alter DNA repair activity. Upregulation of some DNA repair activities was also observed in several of the treated samples, suggesting activation of compensatory signaling pathways upon treatment. The data collectively indicate that mutations in the BRAF and NRAS genes exert distinct regulatory effects on the excision/synthesis steps of the BER and NER pathways and that targeted pharmacological inactivation of the signaling mechanism can translate into specific consequences in DNA repair capacity. The heterogeneity of the responses reported herein could help define subtypes of melanoma that are associated with resistance to targeted therapies.

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