Photo-conversion of two epimers (20R and 20S) of pregna-5,7-diene-3β, 17α, 20-triol and their bioactivity in melanoma cells

Michal A. Zmijewski, Wei Li, Jordan K. Zjawiony, Trevor W. Sweatman, Jianjun Chen, Duane Miller, Andrzej T. Slominski

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Pregna-5,7-dienes and their hydroxylated derivatives can be formed in vivo when there is a deficiency in 7-dehydrocholesterol (7-DHC) Δ-reductase function, e.g., Smith-Lemli-Opitz syndrome (SLOS). Ultraviolet B (UVB) radiation induces photoconversion of 7-DHC to vitamin D3, lumisterol3 and tachysterol3. Two epimers (20R and 20S) of pregna-5,7-diene-3β,17α,20-triol (4R and 4S, respectively) were synthesized and their UVB photo-conversion products identified as corresponding 9,10-secosteroids with vitamin D-like and tachysterol-like structures, and 5,7-dienes with inverted configuration at C-9 and C-10 (lumisterol-like). The number and character of the products and the dynamics of the process were dependent on the UVB dose. At high UVB doses, the formation of multiple oxidized derivatives of the primary products, and the formation of 5,7,9(11)-triene, were observed. The production of vitamin D-like, tachysterol-like and lumisterol-like derivatives was also observed in human skin treated with 4R and 4S, and subjected to UV irradiation, as shown by RP-HPLC. Newly synthesized compounds inhibited melanoma growth in dose dependent manner, and some of them showed equal or higher potency than 1,25(OH)2D3. In summary, we have characterized for the first time the products of UV induced conversion of pregna-5,7-diene-3β,17α,20-triols and documented that the newly synthesized compounds have antiproliferative properties against melanoma cells.

Original languageEnglish (US)
Pages (from-to)218-228
Number of pages11
JournalSteroids
Volume74
Issue number2
DOIs
StatePublished - Feb 1 2009

Fingerprint

Smith-Lemli-Opitz Syndrome
Ergosterol
Bioactivity
Vitamin D
Melanoma
Secosteroids
Derivatives
Cholecalciferol
High Pressure Liquid Chromatography
Radiation
Skin
Growth
Irradiation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Photo-conversion of two epimers (20R and 20S) of pregna-5,7-diene-3β, 17α, 20-triol and their bioactivity in melanoma cells. / Zmijewski, Michal A.; Li, Wei; Zjawiony, Jordan K.; Sweatman, Trevor W.; Chen, Jianjun; Miller, Duane; Slominski, Andrzej T.

In: Steroids, Vol. 74, No. 2, 01.02.2009, p. 218-228.

Research output: Contribution to journalArticle

Zmijewski, Michal A. ; Li, Wei ; Zjawiony, Jordan K. ; Sweatman, Trevor W. ; Chen, Jianjun ; Miller, Duane ; Slominski, Andrzej T. / Photo-conversion of two epimers (20R and 20S) of pregna-5,7-diene-3β, 17α, 20-triol and their bioactivity in melanoma cells. In: Steroids. 2009 ; Vol. 74, No. 2. pp. 218-228.
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AU - Li, Wei

AU - Zjawiony, Jordan K.

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AU - Slominski, Andrzej T.

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