Abstract 2085: Reactive oxygen species promote signaling in neuroblastoma cells

Neuroblastoma is a rare cancer of the sympathetic nervous system that is commonly diagnosed in children before the age of five. Neuroblastoma affects 1 out of 100,000 children and about 700 new cases of neuroblastoma each year. Most cases of neuroblastoma begin in the abdomen in the adrenal gland, or next to spinal cord and in the chest. Neuroblastoma is known to spread to the bones, face, skull, pelvis, shoulder, arms, legs, bone marrow, liver, lymph nodes, skin and around the eyes. Currently, there is no explanation for the cause of neuroblastoma. Our lab seeks to understand the mechanisms used for these cells to metastasize. The Erk pathway, part of the mitogen activated protein kinases, helps to regulate the cell cycle, proliferation, invasion and metastasis. The PI3k/Akt pathway regulates cell growth, survival, and activation of transcription factors such as hypoxia inducible factors (HIFs). Hypoxia is a state where the cell is experiencing a lower than normal oxygen tension activating HIF-1 alpha and HIF-2 to cause an expression of target genes for angiogenesis, (generation of new blood cells), erythropoiesis (formation of new blood cells), and glucose transport into cells enabling them to survive under hypoxic conditions and acquire access to an oxygen supply. Hypoxia increases reactive oxygen species used to stabilize HIF-1 alpha. Reactive oxygen species generation is dependent on oxygen induced changes in the redox state of the electron transport chain. Low levels of reactive oxygen species can regulate controlled proliferation. However, high levels of reactive oxygen species lead to DNA damage and genomic instability by activating these signaling pathways stopping cell death in senescence leading to uncontrolled proliferation. Therefore, our hypothesis is that low levels of reactive oxygen species promote neuroblastoma cell survival through upregulation of survival signaling, whereas high levels of reactive oxygen species induce neuroblastoma cell apoptosis. To test this idea, we exposed an aggressive, metastatic cell lines, IMR 32 neuroblastoma cells, to increasing concentrations of hydrogen peroxide, used to induce reactive oxygen species formation. Cells were analyzed morphologically for apoptosis. With increasing concentrations of hydrogen peroxide, IMR32 neuroblastoma cells round up and become less adherent. High doses of hydrogen peroxide induce cell fragmentation indicative of apoptosis. We are currently investigating the effect of hydrogen peroxide on the induction of caspase-3, a proapoptotic molecule, and DNA fragmentation, measured by TUNEL assay. Our data suggest that reactive oxygen species induce apoptosis in human neuroblastoma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2085. doi:10.1158/1538-7445.AM2011-2085