Late ROS accumulation and radiosensitivity in SOD1-overexpressing human glioma cells

Z, Gao; Sarsour, Ehab H.; Kalen, Amanda L.; Li, Ling; Kumar, Maneesh G.; Goswami, Prabhat C.

doi:10.1016/j.freeradbiomed.2008.08.009

Cited by 60 publications

(64 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hh signaling also seems to protect neurons against oxidative stress by upregulation of SOD and glutathione peroxidase (Dai et al 2011, Ji et al 2012. Furthermore, SOD1-overexpressing glioma cells are less sensitive to radiation and SOD1 is upregulated in neuronal stem cells (Gao et al 2008). Consistent with our findings, several GLI1 target genes including proto-oncogenes CXCR4, BMI1 and BCL-2 and cyclins D1, D2 and E1 have been shown to contribute to pituitary adenoma pathogenesis.…”

Section: Discussionsupporting

confidence: 89%

The role of proto-oncogene GLI1 in pituitary adenoma formation and cell survival regulation

Lampichler¹,

Ferrer²,

Vila³

et al. 2015

Endocrine-Related Cancer

View full text Add to dashboard Cite

The Hedgehog (Hh) pathway is an important regulator of early tissue patterning and stem cell propagation. It was found to be aberrantly activated in numerous types of human cancer and might be relevant in cancer stem cells. The identification of adult stem cells in the pituitary raised the question if tumor-initiating cells and Hh signaling are involved in pituitary adenoma formation. The present study aimed at the evaluation of Hh signaling in relation to stem cell and cell cycle markers in 30 human pituitary adenomas and in cultured murine adenoma cells. Therefore, expression levels of components of the Hh pathway, stem cell marker SOX2, cell cycle regulator tumor-protein 53 (TP53), proliferation marker Ki67 (MKI67) and superoxide dismutase 1 (SOD1) were evaluated in 30 human pituitary adenomas in comparison to control tissue. Modulation of cell function and target gene expression by the inhibition and activation of the Hh pathway were studied in murine adenoma cells. We show that transcription factor glioma-associated oncogene 1 (GLI1) is overexpressed in 87% of all pituitary adenomas. The expression of GLI1 significantly correlated with that of SOX2, TP53, MKI67 and SOD1. Inhibition of GLI1 resulted in the downregulation of the above genes and severe cell death in mouse adenoma cells. On the other hand, activation of the Hh pathway increased cell viability and target gene expression. In conclusion, our findings point toward an alternative, ligand-independent Hh pathway activation with GLI1 playing a major role in the cell survival of pituitary adenoma cells.

show abstract

Section: Discussionsupporting

confidence: 89%

The role of proto-oncogene GLI1 in pituitary adenoma formation and cell survival regulation

Lampichler¹,

Ferrer²,

Vila³

et al. 2015

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…36 Overall ROS levels were determined by quantifying H 2 DCFDA fluorescence intensity. As previously shown, I-JIP and SP600125 each increased H 2 DCFDA fluorescence intensity in control cultures (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…24 As increased oxidative stress represents a primary mechanism contributing to IR-induced cell death, 25, 26, 36 we hypothesized that the ability of JNK to suppress ROS contributes to the relative radioresistance of VS cells. Alternatively, JNK activity, which promotes VS cell proliferation, may increase VS cell radiosensitivity, similar to the effects of mitogenic ErbB2 ligands.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of c-Jun N-Terminal Kinase Activity Enhances Vestibular Schwannoma Cell Sensitivity to Gamma Irradiation

Clark

Telisak

et al. 2013

Neurosurgery

View full text Add to dashboard Cite

Background Radiosurgery is increasingly used to treat vestibular schwannomas (VSs). Increasing the sensitivity of VS cells to irradiation (IR) could allow for lower and/or more effective doses of IR, improving safety and efficacy. Persistent JNK activity in VS cells reduces cell death by suppressing accumulation of reactive oxygen species (ROS) raising the possibility that JNK activity protects against IR-induced VS cell death, which is mediated by ROS. Objective Determine the extent to which JNK signaling contributes to VS cell radiosensitivity. Methods Primary human VS cultures, derived from acutely resected tumors, received single doses (5–40 Gy) of γ-irradiation. Histone 2AX phosphorylation, a marker of IR-induced DNA damage, was assayed by western blot and immunostaining. ROS levels were quantified by measuring 2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA) fluorescence. Cell apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling. Results The JNK inhibitors, SP6000125 and I-JIP, reduced H2AX phosphorylation following IR. They also increased H2DCFDA fluorescence in non-irradiated cultures and significantly increased IR-induced (5–10 Gy) H2DCFDA fluorescence 72 hours, but not 2 hours, after IR. Finally, I-JIP (50 µM) significantly increased VS cell apoptosis in cultures treated with 20–40 Gy. I-JIP (20 µM), SP600125 (20 µM), and JNK1/2 siRNA knock-down each increased VS cell apoptosis in cultures treated with 30–40 Gy, but not lower doses, of IR. Conclusions Inhibition of JNK signaling decreases H2AX phosphorylation and increases ROS and apoptosis in VS cells following γ-irradiation. These results raise the possibility of using JNK inhibitors to increase the effectiveness of radiosurgery for treatment of VSs.

show abstract

“…In fact, ionizing radiation can trigger waves of self-inflicted oxidative stress with DNA and tissue damage that can persist for weeks and months after exposure. 134,163,[181][182][183] These effects are associated with inflammatory cytokine production. 174 Senescent cells can be detected in vitro by a hallmark increase in p16 INK4a , p21 CIP1 , and β-galactosidase expression.…”

Section: Persistent Damage Ros and Senescencementioning

confidence: 99%

Opportunities and challenges of radiotherapy for treating cancer

2015

View full text Add to dashboard Cite

The past 20 years have seen dramatic changes in the delivery of radiation therapy, but the impact of radiobiology on the clinic has been far less substantial. A major consideration in the use of radiotherapy has been on how best to exploit differences between the tumour and host tissue characteristics, which in the past has been achieved empirically by radiation-dose fractionation. New advances are uncovering some of the mechanistic processes that underlie this success story. In this Review, we focus on how these processes might be targeted to improve the outcome of radiotherapy at the individual patient level. This approach would seem a more productive avenue of treatment than simply trying to increase the radiation dose delivered to the tumour.

show abstract

Late ROS accumulation and radiosensitivity in SOD1-overexpressing human glioma cells

Cited by 60 publications

References 36 publications

The role of proto-oncogene GLI1 in pituitary adenoma formation and cell survival regulation

The role of proto-oncogene GLI1 in pituitary adenoma formation and cell survival regulation

Inhibition of c-Jun N-Terminal Kinase Activity Enhances Vestibular Schwannoma Cell Sensitivity to Gamma Irradiation

Opportunities and challenges of radiotherapy for treating cancer

Contact Info

Product

Resources

About