Growth-Inhibition of Human-Melanoma Cells by Vitamin-D Analogs

Brenner, Rv; Shabahang, Mohsen; Houghton, Am; Nauta, Rj; Uskokovic,; Schumaker, Lisa M.; Buras, Rr; Evans, Srt

doi:10.3892/or.2.6.1157

Cited by 4 publications

(3 citation statements)

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“…Since antimelanoma properties of vitamin D and its analogs were reviewed recently (38,130), what follows is only a short overview. Colston and co-workers showed VDR-expressing melanoma cells were inhibited by 1,25(OH) 2 D 3 (124) (187)(188)(189)(190), RPMI 7951 (191,192), SM (189), SK Mel 28 (189,(192)(193)(194) and WM1341 (187,188). The anticancer activity of calcitriol was also demonstrated against mouse B16 and hamster Bomirski melanoma cells (195).…”

Section: Effects Of Vitamin D On Melanoma Cells In Vitromentioning

confidence: 97%

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

2019

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Melanoma is one of the most lethal types of skin cancer, with a poor prognosis once the disease enters metastasis. The efficacy of currently available treatment schemes for advanced melanomas is low, expensive, and burdened by significant side-effects. Therefore, there is a need to develop new treatment options. Skin cells are able to activate vitamin D via classical and non-classical pathways. Vitamin D derivatives have anticancer properties which promote differentiation and inhibit proliferation. The role of systemic vitamin D in patients with melanoma is unclear as epidemiological studies are not definitive. In contrast, experimental data have clearly shown that vitamin D and its derivatives have anti-melanoma properties. Furthermore, molecular and clinicopathological studies have demonstrated a correlation between defects in vitamin D signaling and progression of melanoma and disease outcome. Therefore, adequate vitamin D signaling can play a role in the treatment of melanoma. Skin cells are able to activate vitamin D via classical and nonclassical metabolic pathways (1-9). Vitamin D derivatives have anticancer properties and promote differentiation and inhibit proliferation of various cells, including melanoma, the most aggressive and lethal type of skin cancer. In this review, we provide an overview on the endogenous synthesis and activation of vitamin D via classical and non-classical pathways. We also present the association of vitamin D and melanoma based on epidemiological, experimental and clinical evidence, showing that defects in vitamin D signaling correlate with progression of melanoma and disease outcome. Therefore, restoration of the adequate vitamin D signaling can play a role in melanoma therapy. 473 This article is freely accessible online.

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Section: Effects Of Vitamin D On Melanoma Cells In Vitromentioning

confidence: 97%

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

2019

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“…239 This observation was supported by the description of vitamin D metabolism in melanoma cells. 240,241 Further studies showed that vitamin D inhibited the growth of several melanoma cell lines, including: human: A375, 242 ME18, 243 MeWo, 244–246 RPMI 7951, 247,248 SK Mel 28, 247,249,250 SKMEL-188, WM35 and WM1341; 39,40,64,118,119,242,251 mouse B16; 67,252,253 and hamster Bomirski melanomas. 67,118 Furthermore, 1,25(OH) 2 D3 inhibited anchorage-independent growth and plating efficiency of human SKMEL-188, hamster AbC1, 39,64,118 and murine B16 (ref.…”

Section: Vitamin D and Experimental Models Of Melanomamentioning

confidence: 99%

Vitamin D signaling and melanoma: role of vitamin D and its receptors in melanoma progression and management

Slominski

Brożyna

Żmijewski

et al. 2017

Laboratory Investigation

114

128

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Ultraviolet B (UVB), in addition to having carcinogenic activity, is required for the production of vitamin D3 (D3) in the skin which supplies >90% of the body's requirement. Vitamin D is activated through hydroxylation by 25-hydroxylases (CYP2R1 or CYP27A1) and 1α-hydroxylase (CYP27B1) to produce 1,25(OH)2D3, or through the action of CYP11A1 to produce mono-di- and trihydroxy-D3 products that can be further modified by CYP27B1, CYP27A1, and CYP24A1. The active forms of D3, in addition to regulating calcium metabolism, exert pleiotropic activities, which include anticarcinogenic and anti-melanoma effects in experimental models, with photoprotection against UVB-induced damage. These diverse effects are mediated through an interaction with the vitamin D receptor (VDR) and/or as most recently demonstrated through action on retinoic acid orphan receptors (ROR)α and RORγ. With respect to melanoma, low levels of 25(OH)D are associated with thicker tumors and reduced patient survival. Furthermore, single-nucleotide polymorphisms of VDR and the vitamin D-binding protein (VDP) genes affect melanomagenesis or disease outcome. Clinicopathological analyses have shown positive correlation between low or undetectable expression of VDR and/or CYP27B1 in melanoma with tumor progression and shorter overall (OS) and disease-free survival (DFS) times. Paradoxically, this correlation was reversed for CYP24A1 (inactivating 24-hydroxylase), indicating that this enzyme, while inactivating 1,25(OH)2D3, can activate other forms of D3 that are products of the non-canonical pathway initiated by CYP11A1. An inverse correlation has been found between the levels of RORα and RORγ expression and melanoma progression and disease outcome. Therefore, we propose that defects in vitamin D signaling including D3 activation/inactivation, and the expression and activity of the corresponding receptors, affect melanoma progression and the outcome of the disease. The existence of multiple bioactive forms of D3 and alternative receptors affecting the behavior of melanoma should be taken into consideration when applying vitamin D management for melanoma therapy.

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“…One of these modifiers, the biologically active form of the seco-steroid hormone vitamin D3, is la,25-dihydroxyvitamin D3 (la,25(OH)2D3), and it can inhibit the growth and/or induce differentiation in vitro of cancer cells from several different tissues types (Norman et al 1990, Shabahang et al 1994 Hematology/Oncology, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, California 90048, USA 'Hoffman La Roche, Nutley, New Jersey 07110, USA (Requests for offprints should be addressed to M J Campbell, Department of Immunology, Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK) Naveilhan et al 1994, Pakkala et al 1995, Brenner et al 1995, Wali et al 1995. Prostate primary malignant tissue (Peehl et al 1994) and some cell lines (Skowronski et al 1993, Schwartz et al 1994 have been shown also to have their growth inhibited by la,25(OH)2D3.…”

Section: Introductionmentioning

confidence: 98%

Inhibition of proliferation of prostate cancer cells by a 19-nor-hexafluoride vitamin D3 analogue involves the induction of p21waf1, p27kip1 and E-cadherin

Campbell

Elstner²,

Holden³

et al. 1997

Journal of Molecular Endocrinology

175

126

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We have synthesized and studied the ability of a series of seven novel 1 alpha,25(OH)2 vitamin D3 analogues to inhibit clonal growth of prostate cancer cells (LNCaP, PC-3 and DU-145). Addition of double and triple bonds to the C/D ring (C-16) and side chain (C-22 and C-23) as well as lengthening of the side chain were important for enhanced activity against LNCaP and PC-3. Reorientation of the side chain in the 20-epi configuration resulted in analogues that were extremely potent only against LNCaP (ED50 approximately 5 x 10(-11) M). Compounds with six fluorines on the end of the side chain were very active against both PC-3 and LNCaP (ED50 approximately 2 x 10(-8) M). DU-145 cells were relatively resistant to compounds with all of these modifications, but removal of C-19 (e.g. 1,25(OH)2-16-ene-23-yne-26,27-F6-19-nor-D3) resulted in an analogue that was inhibitory against all three prostate cell lines. Further analysis showed that pulse exposure (3 days, 10(-7) M) to this analogue was enough to inhibit clonal growth of PC-3 cells by 50%. The same exposure also induced cell cycle arrest of all three cell lines, accompanied by upregulated protein expression of the cyclin-dependent kinase inhibitor (CDKI) known as p21waf1 in all three cell lines, and the CDKI known as p27kip1 in LNCaP cells. Associated with upregulation of these CDKIs, partial differentiation occurred as measured by increased expression of both prostate-specific antigen by LNCaP cells and E-cadherin, a cell adhesion protein that may act as a putative tumour suppressor (LNCaP and PC-3 cells). In summary, this is the first report of a potent series of 19-nor-vitamin D3 analogues with the ability to inhibit proliferation of LNCaP, PC-3 and DU-145 prostate cancer cell lines. These compounds may mediate their potent anti-proliferative activities through a cell cycle arrest pathway.

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Growth-Inhibition of Human-Melanoma Cells by Vitamin-D Analogs

Cited by 4 publications

References 0 publications

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

Relevance of Vitamin D in Melanoma Development, Progression and Therapy

Vitamin D signaling and melanoma: role of vitamin D and its receptors in melanoma progression and management

Inhibition of proliferation of prostate cancer cells by a 19-nor-hexafluoride vitamin D3 analogue involves the induction of p21waf1, p27kip1 and E-cadherin

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