Temporal relationship of CDK1 activation and mitotic arrest to cytosolic accumulation of cytochrome C and caspase-3 activity during Taxol-induced apoptosis of human AML HL-60 cells

Ibrado, Ana Maria; Kim, C. N.; Bhalla, Kapil N.

doi:10.1038/sj.leu.2401218

Cited by 69 publications

(50 citation statements)

References 21 publications

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“…Paclitaxel-induced apoptosis has been reported to be associated with changes in mitochondrial transmembrane potential, mitochondrial release of cytochrome c, activation of caspase 3 and cleavage of PARP (Ibrado et al, 1998;Scarlett et al, 2000). Our results show strongly reduced Bcl-2 levels and only weakly reduced Bax levels in the mut-p53 cells in comparison to wt-p53 cells.…”

Section: Discussionsupporting

confidence: 50%

Inactivation of wild-type p53 by a dominant negative mutant renders MCF-7 cells resistant to tubulin-binding agent cytotoxicity

et al. 2001

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SummaryThe present study was performed to gain insight into the role of p53 on the cytotoxicity of tubulin-binding agents (TBA) on cancer cells. Drug sensitivity, cell cycle distribution and drug-induced apoptosis were compared in 2 lines derived from the mammary adenocarcinoma MCF-7: the MN-1 cell line containing wild-type p53 (wt-p53) and the MDD2 line, containing a dominant negative variant of the p53 protein (mut-p53). The MDD2 cell line was significantly more resistant to the cytotoxic effects of vinblastine and paclitaxel than the MN1 cell line. MN1 cells, but not MDD2 cells, displayed wt-p53 protein accumulation as well as p21/WAF1 and cyclin G1 induction after exposure to TBA. Both cell lines arrested at G 2 /M after drug treatment. However exposure of MN1 cells to TBA resulted in a stronger variation in mitochondrial membrane potential, associated with cleavage of PARP, and more apoptosis, as measured by annexin V expression. After exposure to vinblastine, Raf 1 kinase activity was reduced in MDD2 cells but not in MN1 cells. Addition of flavopiridol to vinblastine-and paclitaxel-treated cells reversed the MDD2-resistant phenotype by inducing G 1 cell cycle arrest and inhibiting endoreduplication. We conclude that the p53 status of cancer cells influences their sensitivity to TBA cytotoxicity. This effect is likely to involve differences in the apoptotic cascade.

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Section: Discussionsupporting

confidence: 50%

Inactivation of wild-type p53 by a dominant negative mutant renders MCF-7 cells resistant to tubulin-binding agent cytotoxicity

et al. 2001

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“…The involvement of caspase-3 in the apoptotic response to RanBP1 downregulation is interesting in light of the notion that taxol, which suppresses MT dynamics and causes prometaphase arrest, also induces caspase-3 activation and eventually apoptosis (Ibrado et al, 1998;Oyaizu et al, 1999;Wieder et al, 2001;Lu et al, 2005;Impens et al, 2008). We therefore decided to investigate the combined effect of RanBP1 interference and taxol exposure.…”

Section: Downregulation Of Ranbp1 Levels Render U2os Cells More Sensimentioning

confidence: 99%

RanBP1 downregulation sensitizes cancer cells to taxol in a caspase-3-dependent manner

et al. 2009

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Mitotic microtubule (MT)-targeting drugs are widely used to treat cancer. The GTPase Ran regulates multiple processes, including mitotic spindle assembly, spindle pole formation and MT dynamics; Ran activity is therefore essential to formation of a functional mitotic apparatus. The RanBP1 protein, which binds Ran and regulates its interaction with effectors, is overexpressed in many cancer types. Several observations indicate that RanBP1 contributes to regulate the function of the mitotic apparatus: RanBP1 inactivation yields hyperstable MTs and induces apoptosis during mitosis, reminiscent of the effects of the MT-stabilizing drug taxol. Here we have investigated the influence of RanBP1 on spontaneous and taxol-induced apoptosis in transformed cells. We report that RanBP1 downregulation by RNA interference activates apoptosis in several transformed cell lines regardless of their p53 status, but not in the caspase-3-defective MCF-7 breast cancer cell line. Furthermore, RanBP1-interfered cells show an increased apoptotic response to taxol compared to their counterpart with normal or high RanBP1 levels, and this response is caspase-3 dependent. These results indicate that RanBP1 can modulate the outcome of MT-targeting therapeutic protocols.

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“…Paclitaxel-initiated apoptosis has been associated with activation of p34 cdc2 , [67][68][69][70] Cdc2-like kinase, 46 and other cyclin-dependent kinases (Cdks). 57,71,72 Recent studies indicate that catastrophically activated Cdks are among the terminal effectors of the apoptotic process, 73,74 also supporting a close association between p34 cdc2 activation and apoptosis in paclitaxel-treated cells.…”

Section: Apoptosis By Aberrant Activation Of Cyclin-dependent Kinasesmentioning

confidence: 99%

“…13 It is noteworthy that low (20 nM) concentrations of paclitaxel have been shown to be able to accelerate progression of the cell cycle, further facilitating the final G 2 /M arrest. 97 Cells arrested at the G 2 /M phase are characterized by p34 cdc2 activation [67][68][69][70] and Bcl-2 phosphorylation, 40 -43 which both contribute to apoptosis. The duration of normal mitosis varies from 45 minutes to about 3 hours.…”

Section: Cells Treated With Low Concentrations Of Paclitaxelmentioning

confidence: 99%

Paclitaxel-induced cell death

Wang

Soong

2000

Cancer

562

185

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Temporal relationship of CDK1 activation and mitotic arrest to cytosolic accumulation of cytochrome C and caspase-3 activity during Taxol-induced apoptosis of human AML HL-60 cells

Cited by 69 publications

References 21 publications

Inactivation of wild-type p53 by a dominant negative mutant renders MCF-7 cells resistant to tubulin-binding agent cytotoxicity

Inactivation of wild-type p53 by a dominant negative mutant renders MCF-7 cells resistant to tubulin-binding agent cytotoxicity

RanBP1 downregulation sensitizes cancer cells to taxol in a caspase-3-dependent manner

Paclitaxel-induced cell death

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