Anticancer research · 2010
Motexafin gadolinium enhances p53-Mdm2 interactions, reducing p53 and downstream targets in lymphoma cell lines.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Singh Amareshwar T K, Evens Andrew M, Prachand Sheila N, Gordon Leo I
Аннотация
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.
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.