Motexafin gadolinium enhances p53-Mdm2 interactions, reducing p53 and downstream targets in lymphoma cell lines

Amareshwar T.K. Singh, Andrew M. Evens, Sheila N. Prachand, Leo I. Gordon

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Loss of p53 renders cells more susceptible to acute oxidant stress induced by oxidant-generating agents such as motexafin gadolinium (MGd). We hypothesized that reactive oxygen species (ROS)-generating MGd results in low-level p53 expression, making cells more susceptible to oxidant stress. Materials and Methods: Lymphoma cells were incubated with different concentrations of MGd with or without zinc (Zn) and ascorbate, and ROS, apoptosis, proteins, and oxidant genes were measured. Results: MGd, with ascorbate and Zn, induced apoptosis in lymphoma cells. This was accompanied by reduction of p53 protein but not message, and by reduction of p53 downstream targets p21, glutathione peroxidase 1 (GPx1), and p53 up-regulated modulator of apoptosis (PUMA). p53 protein reduction was reversed by MG132, and nutlin-3. Conclusion: Our data are consistent with a pathway of cell death that is independent of p53-mediated induction of PUMA; the cellular response to reduce p53 represents a cell survival adjustment to ROS-mediated stress.

Original languageEnglish (US)
Pages (from-to)1131-1136
Number of pages6
JournalAnticancer Research
Volume30
Issue number4
StatePublished - Apr 1 2010
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Apoptosis
  • Lymphoma
  • Motexafin gadolinium
  • Reactive oxygen species
  • p53

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