Analysis of the Vitamin D system in Cutaneous Malignancies

Kamradt, Jörn; Rafi, Leyla; Mitschele, Tanja; Meineke, Viktor; Гартнер, Барбара; Tilgen, Wolfgang; Holick, Michael F.; Reichrath, Jörg

doi:10.1007/978-3-642-55580-0_19

Cited by 32 publications

(32 citation statements)

References 33 publications

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“…The calculated rates of conversion of [4][5][6][7][8][9][10][11][12][13][14] C]cholesterol into pregnenolone and progesterone in cutaneous mitochondria were 0.14% and 0.04%, respectively, 1% of the conversion reported for placental mitochondria [39]. Pregnenolone was also detected by RIA in the culture medium of skin cells incubated for 18 h with 25 lM 22R-hydroxycholesterol (not shown).…”

Section: Resultsmentioning

confidence: 90%

“…Lastly, when mitochondria from skin cells (immortalized and malignant keratinocytes) were incubated with [4][5][6][7][8][9][10][11][12][13][14] C]cholesterol, it resulted in the production of steroids that migrated at the same rate as the pregnenolone and progesterone standards (not shown). The calculated rates of conversion of [4][5][6][7][8][9][10][11][12][13][14] C]cholesterol into pregnenolone and progesterone in cutaneous mitochondria were 0.14% and 0.04%, respectively, 1% of the conversion reported for placental mitochondria [39].…”

Section: Resultsmentioning

confidence: 99%

“…8. Transformation of 7-DHC (1) to 7-DHP (2), followed by a proposed sequence for the enzymatic transformation of 7-DHP to its hydroxy derivatives (3)(4)(5)(6)(7)(8)(9)(10), and/or to secosteroids (11)(12)(13)(14)(15)(16)(17)(18)(19) generated by the action of UVB radiation. 3, 3b,11a-or b-Dihydroxypregna-5,7-dien-20-one; 4, 3b,17b-dihydroxypregna-5,7-dien-20-one; 5, 3b,21-dihydroxypregna-5,7-dien-20-one; 6, 3b,17b,21-trihydroxypregna-5,7-dien-20-one; 7, 3b,11a-or 11b,21-trihydroxypregna-5,7-diene-20-one; 8, 3b,11a-or 11b,17-trihydroxypregna-5,7-diene-20-one; 9, 3b,11a-or b,17b,21-tetrahydroxypregna-5,7-dien-20-one; 10, 3b,20a-or b-dihydroxypregna-5,7-diene; 11, 5Z,7E-3b-hydroxy-9,10-secopregna-5,7,10(19)trien-20-one; 12, 5Z,7E-3b, 11a-or b-dihydroxy-9,10-secopregna-5,7,10(19)trien-20-one; 13, 5Z,7E-3,17b-dihydroxy-9,10-secopregna-5,7,10(19)trien-20-one; 14, 5Z,7E-3,b,21-dihydroxy-9,10-secopregna-5,7,10(19)trien-20-one; 15, 5Z,7E-3b,17b,21-trihydroxy-9,10-secopregna-5,7,10(19)trien-20-one; 16, 5Z,7E-3b,11a-or 11b,21-trihydroxy-9,10-secopregna-5,7,10(19)trien-20-one; 17, 5Z,7E-3b,11a-or 11b,17-trihydroxy-9,10-secopregna-5,7,10(19)trien-20-one; 18, 5Z,7E-3b,11a-or b,17b,21-tetrahydroxy-9,10-secopregna-5,7,10(19)-trien-20-one; 19, 5Z,7E-3b,11a-or b-dihydroxy-9,10-secopregna-5,7,10(19)triene.…”

Section: Substrate Human P450sccmentioning

confidence: 99%

“…Cutaneous elements can in addition have powerful systemic actions as is the case for vitamin D3 [1], which regulates calcium metabolism, and modulates immune and neuroendocrine activities and proliferation and differentiation in cells of different lineages [4][5][6]. Vitamin D3 is formed from the precursor steroid 7-dehydrocholesterol (7-DHC) localized mostly on the plasma membrane of basal epidermal keratinocytes (80% of skin 7-DHC content).…”

mentioning

confidence: 99%

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A novel pathway for sequential transformation of 7‐dehydrocholesterol and expression of the P450scc system in mammalian skin

Slominski¹,

Zjawiony

Wortsman

et al. 2004

European Journal of Biochemistry

225

343

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Following up on our previous findings that the skin possesses steroidogenic activity from progesterone, we now show widespread cutaneous expression of the full cytochrome P450 side-chain cleavage (P450scc) system required for the intracellular catalytic production of pregnenolone, i.e. the genes and proteins for P450scc enzyme, adrenodoxin, adrenodoxin reductase and MLN64. Functionality of the system was confirmed in mitochondria from skin cells. Moreover, purified mammalian P450scc enzyme and, most importantly, mitochondria isolated from placenta and adrenals produced robust transformation of 7-dehydrocholesterol (7-DHC; precursor to cholesterol and vitamin D3) to 7-dehydropregnenolone (7-DHP). Product identity was confirmed by comparison with the chemically synthesized standard and chromatographic, MS and NMR analyses. Reaction kinetics for the conversion of 7-DHC into 7-DHP were similar to those for cholesterol conversion into pregnenolone. Thus, 7-DHC can form 7-DHP through P450scc side-chain cleavage, which may serve as a substrate for further conversions into hydroxy derivatives through existing steroidogenic enzymes. In the skin, 5,7-steroidal dienes (7-DHP and its hydroxy derivatives), whether synthesized locally or delivered by the circulation, may undergo UVB-induced intramolecular rearrangements to vitamin D3-like derivatives. This novel pathway has the potential to generate a variety of molecules depending on local steroidogenic activity and access to UVB.

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Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Substrate Human P450sccmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

A novel pathway for sequential transformation of 7‐dehydrocholesterol and expression of the P450scc system in mammalian skin

Slominski¹,

Zjawiony

Wortsman

et al. 2004

European Journal of Biochemistry

225

343

View full text Add to dashboard Cite

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“…After the time of the initial submission of this manuscript, we have reported additional findings documenting the critical importance of the vitamin D biosynthetic system in the pathogenesis of various cutaneous malignancies including squamous cell carcinomas and supporting the importance of the vitamin D system in BCCs. 52 We and others have shown that cytokines and other factors that stimulate transmembrane-signaling pathways alter VDR levels in keratinocytes and other cell types in vitro. 53,54 43 and Reichrath.…”

Section: Discussionmentioning

confidence: 96%

Analysis of the vitamin D system in basal cell carcinomas (BCCs)

Mitschele

Diesel

Friedrich

et al. 2004

Laboratory Investigation

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Serum levels of 25‐hydroxy‐vitamin D in patients with oral squamous cell carcinoma: Making a case for chemoprevention

Udeabor

Albejadi

Al‐Shehri

et al. 2020

Clinical & Exp Dental Res

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Objectives Serum level of vitamin D has been used as a predictor for cancer development. We intend to measure the baseline vitamin D level in patients with oral squamous cell carcinoma (OSCC) and to compare same with non‐cancer controls to determine any association. Materials and methods Patients with OSCC presenting to our clinics were included in this study. Their baseline serum vitamin D levels were measured prior to cancer treatment after obtaining their consents. These patients were then matched with at least 2 cancer‐free subjects to serve as controls and whose serum vitamin D levels were also measured. The serum vitamin D levels obtained for the two groups were then categorized into normal (>35 ng/ml), mild deficiency (25–35 ng/ml), moderate deficiency (12.5–25 ng/ml), and severe deficiency (<12.5 ng/ml). The data were analyzed statistically and the two groups compared. Results A total of 51 patients with OSCC (Male 22 [43%] and female 29 [57%]) and 113 cancer‐free controls (Male 36 [31.86%] and female 77 [68.14%]) were included in the study. The commonest site for OSCC was the tongue, accounting for 45% of the cancer cases. Mean age for cancer patients was 59.33 years ±12.54 and 49.24 years ±15.79 for the control. Among the OSCC patients, 74.51% had moderate to severe vitamin D deficiencies, whereas only 20.35% had a moderate deficiency in the control group with no severe deficiency. Conclusion Logistic regression analysis shows a positive association between vitamin D deficiency and OSCC risk especially in levels below 25 ng/ml. This further corroborates the assertion that vitamin D deficiency may be a useful indicator of OSCC. It may, therefore, be necessary to routinely prescribe vitamin D supplements to subjects with moderate to severe deficiencies in order to decrease the chances of OSCC development.

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Analysis of the Vitamin D system in Cutaneous Malignancies

Cited by 32 publications

References 33 publications

A novel pathway for sequential transformation of 7‐dehydrocholesterol and expression of the P450scc system in mammalian skin

A novel pathway for sequential transformation of 7‐dehydrocholesterol and expression of the P450scc system in mammalian skin

Analysis of the vitamin D system in basal cell carcinomas (BCCs)

Serum levels of 25‐hydroxy‐vitamin D in patients with oral squamous cell carcinoma: Making a case for chemoprevention

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