Temozolomide reduces the metastatic potential of lewis lung carcinoma (3LL) in mice: Role of α-6 integrin phosphorylation

L. Tentori, C. Leonetti, A. Aquino

Research output: Contribution to journalArticlepeer-review

Abstract

The involvement of protein kinase c (PKC) in the mechanism underlying the antimetastatic properties of triazenes was studied in C57BL/6 mice bearing Lewis lung carcinoma (3LL). In vivo and in vitro treatment with temozolomide, an in-vitro active analogue of dacarbazine, or calphostin c produced a concentration-dependent reduction of spontaneous and artificial metastases. Both agents reduced the ability of 3LL cells to adhere to endothelium. Diethylaminoethyl (DEAE)-sepharose chromatography of cell extracts revealed that incubation of 3LL cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) caused a rapid translocation of protein kinase c activity from cytosol to the membrane fraction. Membrane PKC activity induced by TPA was reduced by 60% after treatment with temozolomide. Coincident with these changes, TPA induced phosphorylation of α-6 integrin, whereas temozolomide or calphostin c abolished the appearance of this phosphoprotein. These results suggest that temozolomide reduced metastatic potential by interfering with α-6 phosphorylation induced by PKC activation.

Original languageEnglish
Pages (from-to)746-754
Number of pages9
JournalEuropean Journal of Cancer
Volume31
Issue number5
DOIs
Publication statusPublished - 1995

Keywords

  • calphostin c
  • cell adhesion
  • integrins
  • metastasis
  • phosphorylation
  • PKC
  • temozolomide

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Hematology

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