Perifosine selectively induces cell cycle block and modulates retinoblastoma and E2F1 protein levels in p53 mutated leukemic cell lines |
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| Authors: | Claudio Celeghini Rebecca Voltan Erika Rimondi Valter Gattei Giorgio Zauli |
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| Affiliation: | (1) Department of Biomedicine, University of Trieste, Trieste, Italy;(2) Department of Life Sciences, University of Trieste, Trieste, Italy;(3) Department of Morphology and Embryology, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, Italy;(4) Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, PN, Italy; |
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| Abstract: | The effect of the single-chain alkylphospholipid perifosine was analyzed in p53wild-type (SKW6.4, OCI and MOLM), p53mutated (BJAB, MAVER) and p53null (HL-60) leukemic cell lines. Perifosine promoted cytotoxicity with a combination of apoptosis induction in all cell lines and cell cycle block at the G2M checkpoint, which was selectively observed in p53mutated 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 p53wild-type cells. These data indicate that perifosine potentially represents an innovative therapeutic approach for p53mutated hematological malignancies. |
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