A new steroidal 5,7-diene derivative, 3β-hydroxyandrosta-5,7-diene-17β-carboxylic acid, shows potent anti-proliferative activity

Tae Kang Kim, Jianjun Chen, Wei Li, Jordan Zjawiony, Duane Miller, Zorica Janjetovic, Robert C. Tuckey, Andrzej Slominski

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The new steroidal 5,7-diene, 3β-hydroxyandrosta-5,7-diene-17β-carboxylic acid (17-COOH-7DA), was synthesized from 21-acetoxypregnenolone, with the oxidative cleavage of the side chain being dependent on the presence of oxygen. In human epidermal (HaCaT) keratinocytes, 17-COOH-7DA inhibited proliferation in a dose-dependent manner, starting at a dose as low as 10-11 M. This inhibition was accompanied by decreased expression of epidermal growth factor receptor, bcl2 and cyclin E2 mRNAs and by increased expression of involucrin mRNA. Inhibition of proliferation was associated with slowing of the cell cycle in G1/G0 phases but not with cell death. 17-COOH-7DA was significantly more potent than pregnenolone, 17-COOH-pregnenolone, 17-COOCH3-7DA and calcitriol. 17-COOH-7DA also inhibited proliferation of normal human epidermal melanocytes and human and hamster melanoma lines, however, with lower potency than for keratinocytes. In normal human dermal fibroblasts 17-COOH-7DA stimulated proliferation in serum-free media but inhibited it in the presence of 5% serum. 17-COOH-7DA inhibited cell colony formation of human and hamster melanoma cells, and induced monocyte-like differentiation of human HL60 leukemia cells. Thus, the new steroidal 5,7-diene, 17-COOH-7DA, can serve as an inhibitor of proliferation of normal keratinocytes and normal and malignant melanocytes, as a condition-dependent regulator of fibroblast proliferation and a stimulator of leukemia cell differentiation.

Original languageEnglish (US)
Pages (from-to)230-239
Number of pages10
JournalSteroids
Volume75
Issue number3
DOIs
StatePublished - Mar 1 2010

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Derivatives
Keratinocytes
Pregnenolone
Melanocytes
Fibroblasts
Cricetinae
Melanoma
Leukemia
Cell Cycle Resting Phase
Messenger RNA
Cyclins
3-hydroxyandrosta-5,7-diene-17-carboxylic acid
Calcitriol
HL-60 Cells
Serum-Free Culture Media
G1 Phase
Cell death
Epidermal Growth Factor Receptor
Monocytes
Cell Differentiation

All Science Journal Classification (ASJC) codes

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

Cite this

A new steroidal 5,7-diene derivative, 3β-hydroxyandrosta-5,7-diene-17β-carboxylic acid, shows potent anti-proliferative activity. / Kim, Tae Kang; Chen, Jianjun; Li, Wei; Zjawiony, Jordan; Miller, Duane; Janjetovic, Zorica; Tuckey, Robert C.; Slominski, Andrzej.

In: Steroids, Vol. 75, No. 3, 01.03.2010, p. 230-239.

Research output: Contribution to journalArticle

Kim, Tae Kang ; Chen, Jianjun ; Li, Wei ; Zjawiony, Jordan ; Miller, Duane ; Janjetovic, Zorica ; Tuckey, Robert C. ; Slominski, Andrzej. / A new steroidal 5,7-diene derivative, 3β-hydroxyandrosta-5,7-diene-17β-carboxylic acid, shows potent anti-proliferative activity. In: Steroids. 2010 ; Vol. 75, No. 3. pp. 230-239.
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AB - The new steroidal 5,7-diene, 3β-hydroxyandrosta-5,7-diene-17β-carboxylic acid (17-COOH-7DA), was synthesized from 21-acetoxypregnenolone, with the oxidative cleavage of the side chain being dependent on the presence of oxygen. In human epidermal (HaCaT) keratinocytes, 17-COOH-7DA inhibited proliferation in a dose-dependent manner, starting at a dose as low as 10-11 M. This inhibition was accompanied by decreased expression of epidermal growth factor receptor, bcl2 and cyclin E2 mRNAs and by increased expression of involucrin mRNA. Inhibition of proliferation was associated with slowing of the cell cycle in G1/G0 phases but not with cell death. 17-COOH-7DA was significantly more potent than pregnenolone, 17-COOH-pregnenolone, 17-COOCH3-7DA and calcitriol. 17-COOH-7DA also inhibited proliferation of normal human epidermal melanocytes and human and hamster melanoma lines, however, with lower potency than for keratinocytes. In normal human dermal fibroblasts 17-COOH-7DA stimulated proliferation in serum-free media but inhibited it in the presence of 5% serum. 17-COOH-7DA inhibited cell colony formation of human and hamster melanoma cells, and induced monocyte-like differentiation of human HL60 leukemia cells. Thus, the new steroidal 5,7-diene, 17-COOH-7DA, can serve as an inhibitor of proliferation of normal keratinocytes and normal and malignant melanocytes, as a condition-dependent regulator of fibroblast proliferation and a stimulator of leukemia cell differentiation.

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