Perifosine selectively induces cell cycle block and modulates retinoblastoma and E2F1 protein levels in p53 mutated leukemic cell lines

Claudio Celeghini, Rebecca Voltan, Erika Rimondi, Valter Gattei, Giorgio Zauli

Research output: Contribution to journalArticle

Abstract

The effect of the single-chain alkylphospholipid perifosine was analyzed in p 53wild-type (SKW6.4, OCI and MOLM), p 53mutated (BJAB, MAVER) and p 53null (HL-60) leukemic cell lines. Perifosine promoted cytotoxicity with a combination of apoptosis induction in all cell lines and cell cycle block at the G 2M checkpoint, which was selectively observed in p 53mutated BJAB and MAVER cell lines. At the molecular level, perifosine induced hypophosphorylation of retinoblastoma protein and the degradation of E2F1 protein in p53mutated but not in p 53wild-type cells. These data indicate that perifosine potentially represents an innovative therapeutic approach for p53mutated hematological malignancies.

Original languageEnglish
Pages (from-to)392-395
Number of pages4
JournalInvestigational New Drugs
Volume29
Issue number2
DOIs
Publication statusPublished - Apr 2011

Keywords

  • Cell cycle
  • P53 status
  • Perifosine
  • Retinoblastoma

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

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