Send to

Choose Destination
See comment in PubMed Commons below
Int J Oncol. 2008 Oct;33(4):677-87.

Low doses of paclitaxel potently induce apoptosis in human retinoblastoma Y79 cells by up-regulating E2F1.

Author information

  • 1Dipartimento di Scienze Biochimiche, Universit√† degli Studi di Palermo, Policlinico, 90127 Palermo, Italy.


Paclitaxel (PTX) is an anticancer drug currently in phase II clinical trials. This study shows for the first time that low doses of PTX (5 nM) potently induce apoptosis in human retinoblastoma Y79 cells. The effect of PTX is accompanied by a potent induction of E2F1 which appears to play a critical role in the effects induced by PTX. PTX induced a dose- and time-dependent effect, with G2/M arrest, cyclines A, E and B1 accumulation and a marked modification in the status of Cdc2-cyclin B1 complex, the major player of the G2/M checkpoint. Apoptosis followed G2/M arrest. An early and prolonged increase in p53 expression with its stabilization by phosphorylation and acetylation and its nuclear translocation occurred. Consistently, PTX increased p21WAF1, bax and MDM2 levels, suggesting that p53 is transcriptionally active. p53 accumulated following both E2F1 up-regulation and increase in the levels of p14ARF which interacts with MDM2 preventing ubiquitination and proteosomal degradation of p53. Both extrinsic (E2F1/Fas/JNK/caspase-2 activation) and intrinsic (Bcl-2 phosphorylation, Bid fragmentation and Bax increase) pathways seemed to be involved. Loss of mitochondrial potential and activation of apoptosome and executive caspase-3,-6 and-7 was shown. Incubation with either the irreversible pan-caspase inhibitors Z-VAD-FMK, or SP600125, a selective inhibitor of JNK, or pifithrin alpha, a potent p53 inhibitor, significantly inhibited the effects induced by PTX.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Spandidos Publications
    Loading ...
    Write to the Help Desk