13-cis retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes

Amanda M. Nelson, Kathryn L. Gilliland, Zhaoyuan Cong, Diane M. Thiboutot

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Isotretinoin (13-cis retinoic acid (13-cis RA)) is the most potent inhibitor of sebum production, a key component in the pathophysiology of acne, yet its mechanism of action remains largely unknown. The effects of 13-cis RA, 9-cis retinoic acid (9-cis RA), and all-trans retinoic acid (ATRA) on cell proliferation, apoptosis, and cell cycle proteins were examined in SEB-1 sebocytes and keratinocytes. 13-cis RA causes significant dose-dependent and time-dependent decreases in viable SEB-1 sebocytes. A portion of this decrease can be attributed to cell cycle arrest as evidenced by decreased DNA synthesis, increased p21 protein expression, and decreased cyclin D1. Although not previously demonstrated in sebocytes, we report that 13-cis RA induces apoptosis in SEB-1 sebocytes as shown by increased Annexin V-FITC staining, increased TUNEL staining, and increased cleaved caspase 3 protein. Furthermore, the ability of 13-cis RA to induce apoptosis cannot be recapitulated by 9-cis RA or ATRA, and it is not inhibited by the presence of a retinoid acid receptor (RAR) pan-antagonist AGN 193109. Taken together these data indicate that 13-cis RA causes cell cycle arrest and induces apoptosis in SEB-1 sebocytes by a RAR-independent mechanism, which contributes to its sebosuppressive effect and the resolution of acne.

Original languageEnglish (US)
Pages (from-to)2178-2189
Number of pages12
JournalJournal of Investigative Dermatology
Volume126
Issue number10
DOIs
StatePublished - Oct 30 2006

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Isotretinoin
Cell Cycle Checkpoints
Cells
Apoptosis
Retinoids
Tretinoin
Acne Vulgaris
Cell Cycle Proteins
Sebum
Acids
Staining and Labeling
Fluorescein-5-isothiocyanate
Annexin A5
Cyclin D1
Cell proliferation
Caspase 3
In Situ Nick-End Labeling
Keratinocytes
Proteins
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

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title = "13-cis retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes",
abstract = "Isotretinoin (13-cis retinoic acid (13-cis RA)) is the most potent inhibitor of sebum production, a key component in the pathophysiology of acne, yet its mechanism of action remains largely unknown. The effects of 13-cis RA, 9-cis retinoic acid (9-cis RA), and all-trans retinoic acid (ATRA) on cell proliferation, apoptosis, and cell cycle proteins were examined in SEB-1 sebocytes and keratinocytes. 13-cis RA causes significant dose-dependent and time-dependent decreases in viable SEB-1 sebocytes. A portion of this decrease can be attributed to cell cycle arrest as evidenced by decreased DNA synthesis, increased p21 protein expression, and decreased cyclin D1. Although not previously demonstrated in sebocytes, we report that 13-cis RA induces apoptosis in SEB-1 sebocytes as shown by increased Annexin V-FITC staining, increased TUNEL staining, and increased cleaved caspase 3 protein. Furthermore, the ability of 13-cis RA to induce apoptosis cannot be recapitulated by 9-cis RA or ATRA, and it is not inhibited by the presence of a retinoid acid receptor (RAR) pan-antagonist AGN 193109. Taken together these data indicate that 13-cis RA causes cell cycle arrest and induces apoptosis in SEB-1 sebocytes by a RAR-independent mechanism, which contributes to its sebosuppressive effect and the resolution of acne.",
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13-cis retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes. / Nelson, Amanda M.; Gilliland, Kathryn L.; Cong, Zhaoyuan; Thiboutot, Diane M.

In: Journal of Investigative Dermatology, Vol. 126, No. 10, 30.10.2006, p. 2178-2189.

Research output: Contribution to journalArticle

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