Desipramine inhibits the growth of a mouse skin squamous cell carcinoma cell line and affects glucocorticoid receptor-mediated transcription

Tatsuya Kinjo, Piotr Kowalczyk, Magdalena Kowalczyk, Zbigniew Walaszek, Tadashi Nishimaki, Thomas J. Slaga, Margaret Hanausek

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The purpose of this study was to examine the effect of tricyclic antidepressant desipramine (DMI) on the growth inhibition and translocation of the glucocorticoid receptor (GR) from the cytoplasm to the nucleus in cancerous and noncancerous cell lines and the effect of DMI on GR-mediated transcription. Nontumorigenic, immortalized keratinocytes cell line (3PC), papilloma (MT1/2), and squamous cell carcinoma (Ca3/7) cell lines were initially used to study the cell growth inhibition by DMI. Although, the growth of all three cell lines was suppressed by DMI, it was more effective in Ca3/7 cells. Therefore, we next examined the effect of DMI on Ca3/7 cells, resistant to growth inhibition by the synthetic glucocorticoid fluocinolone acetonide (FA). DMI inhibited cell proliferation in a time-dependent manner. The translocation of GR was induced by FA alone, DMI alone, and combination of both agents. FA induced GR-mediated transcription in Ca3/7 cells transfected with a luciferase reporter gene under the control of glucocorticoid response element (GRE), but DMI alone did not affect GR-mediated transcription. However, DMI inhibited FA-induced, GR-mediated transcription when both agents were given together. Pretreatment with DMI followed by combination of DMI and FA decreased GR-mediated transcription more than pretreatment with FA. The expression of metallothionein-1 (Mt-1) gene, which is regulated by GR, was induced significantly by the combination of DMI and FA, and enhanced significantly by pretreatment with FA but not DMI. DMI is suggested to inhibit the growth of Ca3/7 cells and to affect GR-mediated transcription.

Original languageEnglish (US)
Pages (from-to)1123-1130
Number of pages8
JournalMolecular Carcinogenesis
Volume48
Issue number12
DOIs
StatePublished - Dec 2009

Keywords

  • Fluocinolone acetonide
  • Glucocorticoid response element
  • Glucocorticoids
  • Metallothionein-1
  • SENCAR mice

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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