Evidence for a High Free Radical State in Low-grade Astrocytomas

Louw, Deon; Bose, Ratna; Sima, Anders A. F.; Sutherland, Garnette R.

doi:10.1097/00006123-199711000-00025

Cited by 29 publications

(25 citation statements)

References 19 publications

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“…The present study showed that TBARS levels in the tested cancerous tissues are higher than those in normal tissues. These reports are coinciding with the earlier data (Louw et al, 1997;Rajeshwar et al, 2005). This emphasizes the reduction in free radical yield and the subsequent decrease in harm and damage to the cell membrane and decrease in MDA production.…”

Section: Discussionsupporting

confidence: 92%

Effect on Inhibition of Proliferation and Antioxidant Enzyme Level of Lippia nodiflora in EAC Cell Line Treated Mice

Ashokkumar¹,

Mazumder²,

Gupta³

et al. 2009

Journal of Complementary and Integrative Medicine

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Objective:The methanol extract of Lippia nodiflora (MELN) (Verbenaceae) was evaluated for antitumor activity against Ehrlich's ascites carcinoma (EAC) bearing Swiss albino mice.Methods: MELN was administered at 200 and 400mg/kg body weight daily for 9 days after 24 h of tumor inoculation. After 18 h fasting, mice were sacrificed. The present study deals with the effect of MELN on the growth of transplantable murine tumor, life span of EAC bearing hosts. Hematological profiles and biochemical parameters were estimated for hepato-renal function and metabolism. Further, Antioxidant enzyme activities were investigated.Results: MELN showed significant (p < 0.001) decrease in tumor volume, packed cell volume and viable cell count and elevated the life span of EAC tumor bearing mice. Hematological profiles reverted to more/less normal levels in extract treated mice. The extract marginally altered serum enzymes, total proteins and bilirubin compared with that of EAC bearing mice. MELN significantly (p < 0.001) decreased the levels of lipid peroxidation and increased the levels of GSH, CAT and SOD. Conclusion:The results of the present study suggest that MELN exhibited significant antitumor activity may be due to the increase of antioxidant activity in EAC bearing mice.

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Section: Discussionsupporting

confidence: 92%

Effect on Inhibition of Proliferation and Antioxidant Enzyme Level of Lippia nodiflora in EAC Cell Line Treated Mice

Ashokkumar¹,

Mazumder²,

Gupta³

et al. 2009

Journal of Complementary and Integrative Medicine

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“…If left uncontrolled, these can harm cell membranes, energy metabolism, and DNA. To prevent such ROS damage, many cancer cells, including gliomas (Louw et al, 1997) show increased synthesis of glutathione (Jefferies et al, 2003) requiring enhanced cystine uptake (Wu et al, 2004). This explains the here-observed high levels of expression of both the catalytic and regulatory subunit of system x c Ϫ in glioma cells from biopsies and in glioma cell lines.…”

Section: System X Cmentioning

confidence: 68%

Inhibition of Cystine Uptake Disrupts the Growth of Primary Brain Tumors

Chung¹,

Lyons²,

Nelson³

et al. 2005

J. Neurosci.

282

298

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Glial cells play an important role in sequestering neuronally released glutamate via Naϩ -dependent transporters. Surprisingly, these transporters are not operational in glial-derived tumors (gliomas). Instead, gliomas release glutamate, causing excitotoxic death of neurons in the vicinity of the tumor. We now show that glutamate release from glioma cells is an obligatory by-product of cellular cystine uptake via system x c Ϫ , an electroneutral cystine-glutamate exchanger. Cystine is an essential precursor for the biosynthesis of glutathione, a major redox regulatory molecule that protects cells from endogenously produced reactive oxygen species (ROS). Glioma cells, but not neurons or astrocytes, rely primarily on cystine uptake via system x c Ϫ for their glutathione synthesis. Inhibition of system x c Ϫ causes a rapid depletion of glutathione, and the resulting loss of ROS defense causes caspase-mediated apoptosis. Glioma cells can be rescued if glutathione status is experimentally restored or if glutathione is substituted by alternate cellular antioxidants, confirming that ROS are indeed mediators of cell death. We describe two potent drugs that permit pharmacological inhibition of system x c Ϫ . One of these drugs, sulfasalazine, is clinically used to treat inflammatory bowel disease and rheumatoid arthritis. Sulfasalazine was able to reduce glutathione levels in tumor tissue and slow tumor growth in vivo in a commonly used intracranial xenograft animal model for human gliomas when administered by intraperitoneal injection. These data suggest that inhibition of cystine uptake into glioma cells through the pharmacological inhibition of system x c Ϫ may be a viable therapeutic strategy with a Food and Drug Administration-approved drug already in hand.

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“…Therefore, the apoptotic effect of NO could be mediated, at least partially, by nitration of some key proteins triggering apoptosis [25,26]. Assuming that SIN-1 can simultaneously generate superoxide and nitric oxide which results in peroxynitrite formation [27], this compound appears as a useful tool to study the role played by protein nitration in peroxynitrite-induced apoptosis of monocytes, although other oxidative changes cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

Specific protein nitration in nitric oxide-induced apoptosis of human monocytes

et al. 2008

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The sustained overproduction of nitric oxide (NO) observed in inflammatory conditions can contribute to cell demise by affecting apoptosis. Nitration of tyrosine residues occurs in a range of diseases involving macrophage activation. Since NO induces apoptosis in monocytes/macrophages, we tested the hypothesis that nitration of specific proteins could result in apoptotic cell death. The peroxynitrite generator SIN-1 promoted apoptosis in monocytes based on oligonucleosomal DNA fragmentation, caspase-3 and -9 activation, Bcl-2 depletion and accumulation of Bax and p53 proteins. We also found that the signaling pathway triggered by SIN-1 was initiated through tyrosine kinase and Rac activation and resulted in increased JNK and p38 activities. Among the tyrosine-nitrated proteins, Rac and Lyn were identified. Using specific inhibitors for different signaling and effector molecules involved in the apoptotic process we demonstrate that NO, via protein-nitration, could play an important role in controlling the inflammatory response by regulation of monocyte homeostasis.

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Evidence for a High Free Radical State in Low-grade Astrocytomas

Cited by 29 publications

References 19 publications

Effect on Inhibition of Proliferation and Antioxidant Enzyme Level of Lippia nodiflora in EAC Cell Line Treated Mice

Effect on Inhibition of Proliferation and Antioxidant Enzyme Level of Lippia nodiflora in EAC Cell Line Treated Mice

Inhibition of Cystine Uptake Disrupts the Growth of Primary Brain Tumors

Specific protein nitration in nitric oxide-induced apoptosis of human monocytes

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