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 language | English (US) |
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Pages (from-to) | 1131-1136 |
Number of pages | 6 |
Journal | Anticancer Research |
Volume | 30 |
Issue number | 4 |
State | Published - Apr 2010 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Keywords
- Apoptosis
- Lymphoma
- Motexafin gadolinium
- Reactive oxygen species
- p53