Inhibitory effects of a luteinizing hormone-releasing hormone agonist on basal and epidermal growth factor-induced cell proliferation and metastasis-associated properties in human epidermoid carcinoma A431 cells

Ying Tang Huang, Jiuan Jiuan Hwang, Lung Ta Lee, Charles Liebow, Ping Ping H. Lee, Ferng Chun Ke, Tung Bin Lo, Andrew V. Schally, Ming Ting Lee

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The purpose of this study was to investigate the effects of a potent LHRH agonist, [D-Trp6]LHRH on the basal and EGF-induced cell proliferation and the metastasis-associated properties in A431 human epidermoid carcinoma. [D-Trp6]LHRH time-dependently inhibited the basal and EGF-stimulated growth of A431 cancer cells. It is assumed that phosphorylation/dephosphorylation of cellular proteins is highly, related to cell growth. This study demonstrates that [D-Trp6]LHRH decreased the basal and EGF-induced total cellular kinase activity, particularly the tyrosine phosphorylation of several cellular proteins including the EGFR. In contrast, [D-Trp6]LHRH did not cause detectable changes in basal and EGF-stimulated serine/threonine phosphorylation of A431 cellular proteins. The inhibitory effect of [D-Trp6]LHRH on A431 cell proliferation was associated with apoptosis as evidenced by the cell morphology and DNA integrity (ladder pattern), the expression of interleukin I βconverting enzyme (ICE) and activation of caspase. Furthermore, EGF could rescue the remaining attached A431 cells following [D-Trp6]LHRH treatment for 48 hr, which suggests that limited exposure to [D-Trp6]LHRH did not channel all cells to irreversible apoptotic process. We also determined the effects of [D-Trp6]LHRH on metastasis-associated properties in A431 cells. [D-Trp6]LHRH reduced both basal and EGF-stimulated secretion of MMP-9 and MMP-2. In addition, [D-Trp6]LHRH suppressed the basal and EGF-induced invasive activity of A431 cells based on an in vitro invasion assay. In conclusion, this study indicates that [D-Trp6]LHRH may act partly through activating tyrosine phosphatase activity to inhibit cell proliferation and the metastasis-associated properties of A431 cancer cells. Our work suggests that [D-Trp6]LHRH may be therapeutically useful in limiting the tumor growth and metastasis of some neoplasms.

Original languageEnglish (US)
Pages (from-to)505-513
Number of pages9
JournalInternational Journal of Cancer
Volume99
Issue number4
DOIs
StatePublished - Jun 1 2002
Externally publishedYes

Keywords

  • [D-Trp]LHRH
  • Apoptosis
  • Interleukin-1β converting enzyme
  • Matrix metalloproteinase
  • Proliferation
  • Protein tyrosine kinase
  • Protein tyrosine phosphatase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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