Perifosine selectively induces cell cycle block and modulates retinoblastoma and E2F1 protein levels in p53 mutated leukemic cell lines.
The effect of the single-chain alkylphospholipid perifosine was analyzed in p53(wild-type) (SKW6.4, OCI and MOLM), p53(mutated) (BJAB, MAVER) and p53(null) (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(2)M checkpoint, which was selectively observed in p53(mutated) BJAB and MAVER cell lines. At the molecular level, perifosine induced hypophosphorylation of retinoblastoma protein and the degradation of E2F1 protein in p53(mutated) but not in p53(wild-type) cells. These data indicate that perifosine potentially represents an innovative therapeutic approach for p53(mutated) hematological malignancies.
Department of Biomedicine, University of Trieste, Trieste, Italy.
Claudio
C
Celeghini
Rebecca
R
Voltan
Erika
E
Rimondi
Valter
V
Gattei
Giorgio
G
Zauli
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D009154:Mutation / Q000235:genetics*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D010767:Phosphorylcholine; C105905:perifosine