NSC109268 potentiates cisplatin-induced cell death in a p53-independent manner

@article{Shankar2010NSC109268PC,
  title={NSC109268 potentiates cisplatin-induced cell death in a p53-independent manner},
  author={Eswar Shankar and Chandreyi Basu and Brett Adkins and Wolfram Siede and Alakananda Basu},
  journal={Journal of Molecular Signaling},
  year={2010},
  volume={5},
  pages={4 - 4}
}
Background Ovarian cancer is the leading cause of death among gynecological cancers. Cisplatin is one of the most effective anticancer drugs used in the treatment of ovarian cancer. Development of resistance to cisplatin limits its therapeutic use. Most of the anticancer drugs, including cisplatin, are believed to kill cancer cells by inducing apoptosis and a defect in apoptotic signaling can contribute to drug resistance. The tumor suppressor protein p53 plays a critical role in DNA damage… 

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References

SHOWING 1-10 OF 49 REFERENCES
Enhancement of cisplatin sensitivity by NSC109268 in budding yeast and human cancer cells is associated with inhibition of S-phase progression
TLDR
The known activities of NSC109268 as proteasome or phosphatase inhibitor could explain the phenotype of S-phase delay by assuming a higher initial DNA damage load, inhibition of DNA translesion synthesis or extended checkpoint arrest.
p53 gene status and chemosensitivity in ovarian cancer.
TLDR
P53 gene status contributes the sensitivity to CDDP in ovarian cancer, and combination treatment of p53 gene transduction and CDDP may be an effective therapeutic modality for ovarian cancer without wild-type p53 genes.
Prolonged wild-type p53 protein accumulation and cisplatin resistance.
TLDR
It is demonstrated that in A2780 and CP70 cells resistance to cisplatin correlates with prolonged p53 protein stabilization and accumulation, and there was no difference in p21WAF-1 half-life between the two cell lines.
Cell death pathways in response to antitumor therapy.
TLDR
It is critically reviewed here how antitumor therapy may elicit the response of human cancers through different cell pathways leading to cell death.
Downregulation of Bid is associated with PKCɛ-mediated TRAIL resistance
TLDR
The results suggest that protein kinase C-ɛ acts upstream of mitochondria and mediates TRAIL resistance via both Bcl-2 and Bid in MCF-7 cells.
Gene expression response to cisplatin treatment in drug-sensitive and drug-resistant ovarian cancer cells
TLDR
The experiments identify p53 as the main pathway producing a large-scale transcriptional response after cisplatin treatment in these cells containing wild-type p53, and knockdown of the p53 protein with small interfering RNA led to a twofold decrease in cell survival in the resistant cells.
Effect of p53 status on sensitivity to platinum complexes in a human ovarian cancer cell line.
TLDR
The results suggest that the loss of functional p53 can increase cisplatin cytotoxicity in A2780, with loss of G(1)/S checkpoint control and decreased cis platin-DNA adduct repair, but these effects can be circumvented by the use of JM335, which forms different DNA-platinum adducts.
Downregulation of Bid is associated with PKCepsilon-mediated TRAIL resistance.
TLDR
The results suggest that PKCepsilon acts upstream of mitochondria and mediates TRAIL resistance via both Bcl-2 and Bid in MCF-7 cells.
A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma.
TLDR
A significant correlation has been found between p53 accumulation, type of mutation, and pathological response to cisplatin-based therapy in ovarian cancer patients, consistent with a role of p53 as a determinant of chemosensitivity of ovarian carcinoma.
Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals
TLDR
It is demonstrated that deletion of the yeast CTR1 gene, which encodes a high-affinity copper transporter, results in increased cis platin resistance and reduced intracellular accumulation of cisplatin, and proposed that cisplin uptake is mediated by the copper transporter Ctr1p in yeast and mammals.
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