Antitumour and pro-apoptotic actions of highly unsaturated fatty acids in glioma

Leaver, H.A.; Bell, Helen; Rizzo, M.T.; Ironside, James W.; Gregor, A.; Wharton, Stephen B.; Whittle, Ian R.

doi:10.1054/plef.2001.0336

Cited by 53 publications

(57 citation statements)

References 26 publications

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“…The presence of either GLA or EPA was found to inhibit C6 rat glioma cell proliferation significantly, as has been reported previously for GLA (Bell et al, 1999;Leaver et al, 2002). However, as the intention of the study was to determine the effects of PUFAs at nontoxic levels, the cells were exposed to concentrations of PUFAs that did not cause greater than ϳ 35% inhibition of proliferation.…”

Section: Discussionmentioning

confidence: 53%

Protective role of glucose‐6‐phosphate dehydrogenase activity in the metabolic response of C6 rat glioma cells to polyunsaturated fatty acid exposure

Ramos

Colquhoun

2003

Glia

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Polyunsaturated fatty acids (PUFAs) can influence tumor growth and migration, both in vitro and in vivo. The PUFA gamma-linolenic acid (GLA) has been reported to improve the poor prognosis associated with human gliomas, although its effects at sublethal concentrations on residual cells postsurgery are poorly understood. The study investigated the effects sublethal PUFA doses (90 or 150 microM) may have on rat C6 glioma cell energy metabolism, since an adequate energy supply is essential for cell proliferation, migration, and apoptosis. Of note was the identification of mitochondrial heterogeneity in relation to the mitochondrial membrane potential (MMP), which has been suggested but unproven in previous studies. GLA and eicosapentaenoic acid (EPA) caused significant changes in cellular fatty acid composition and increased the percentage of cells with a low MMP after a 96-h exposure period. The presence of PUFAs inhibited C6 cell proliferation and migration, although apoptosis was not induced. The protein expression and activity of glucose-6-phosphate dehydrogenase was increased after 96-h incubation with 90 microM GLA and EPA and would allow redox regulation through increased NADPH production, permitting the maintenance of adequate intracellular reduced glutathione concentrations and limiting rates of lipid peroxidation and reactive oxygen species generation. Neither NADP(+)-isocitrate dehydrogenase nor NADP(+)-malate dehydrogenase activity responded to PUFAs, suggesting it is glucose-6-phosphate dehydrogenase that is the principal source of NADPH in C6 cells. These data compliment studies showing that higher concentrations of GLA induced glioma cell death and tumor regression and suggest that GLA treatment could be useful for the inhibition of residual cell proliferation and migration after surgical removal of the tumor mass.

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Section: Discussionmentioning

confidence: 53%

Protective role of glucose‐6‐phosphate dehydrogenase activity in the metabolic response of C6 rat glioma cells to polyunsaturated fatty acid exposure

Ramos

Colquhoun

2003

Glia

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“…In previous studies, we showed that exogenous arachidonic acid limits the growth of human gliomas by inducing apoptosis (49). Thus, it is possible that under conditions in which tumor cells are exposed to excess of arachidonic acid, as may occur in vivo during tumorassociated inflammation, overexpression of mPGES-1 functions as a protective mechanism to convert arachidonic acid -dependent proapoptotic signals into PGE 2 -dependent proliferative signals.…”

Section: Discussionmentioning

confidence: 97%

Microsomal prostaglandin E synthase-1 regulates human glioma cell growth via prostaglandin E2–dependent activation of type II protein kinase A

Payner¹,

Leaver

Knapp

et al. 2006

Molecular Cancer Therapeutics

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Dysregulation of enzymes involved in prostaglandin biosynthesis plays a critical role in influencing the biological behavior and clinical outcome of several tumors. In human gliomas, overexpression of cyclooxygenase-2 has been linked to increased aggressiveness and poor prognosis. In contrast, the role of prostaglandin E synthase in influencing the biological behavior of human gliomas has not been established. We report that constitutive expression of the microsomal prostaglandin E synthase-1 (mPGES-1) is associated with increased prostaglandin E 2 (PGE 2 ) production and stimulation of growth in the human astroglioma cell line U87-MG compared with human primary astrocytes. Consistently, pharmacologic and genetic inhibition of mPGES-1 activity and expression blocked the release of PGE 2 from U87-MG cells and decreased their proliferation. Conversely, exogenous PGE 2 partially overcame the antiproliferative effects of mPGES-1 inhibition and stimulated U87-MG cell proliferation in the absence of mPGES-1 inhibitors. The EP2/EP4 subtype PGE 2 receptors, which are linked to stimulation of adenylate cyclase, were expressed in U87-MG cells to a greater extent than in human astrocytes. PGE 2 increased cyclic AMP levels and stimulated protein kinase A (PKA) activity in U87-MG cells. Treatment with a selective type II PKA inhibitor decreased PGE 2 -induced U87-MG cell proliferation, whereas a selective type I PKA inhibitor had no effect. Taken together, these results are consistent with the hypothesis that mPGES-1 plays a critical role in promoting astroglioma cell growth via PGE 2 -dependent activation of type II PKA.

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“…These researchers demonstrated that CLA strongly inhibits cell growth and proliferation rate, and induce apoptosis. Leaver et al (2002) suggest that intraparenchymal infusion of PUFA may be effective in stimulating glioma regression.…”

Section: Discussionmentioning

confidence: 99%

Chemical composition and antioxidant activity of beebread, and its influence on the glioblastoma cell line (U87MG)

Markiewicz‐Żukowska¹,

Naliwajko²,

Bartosiuk³

et al. 2013

Journal of Apicultural Science

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A b s t r a c t Beebread is processed pollen stored in the cells of the honeycomb, with the addition of various enzymes and honey, which undergoes lactic acid fermentation. Ethanolic extracts (EBBs) were obtained from three different samples of beebread from Poland. Assays were carried out for the determination of chemical composition (GC/MS), for the total phenolic content, and for the antioxidant and cytotoxic activities. The effects of beebread extracts (10, 20, 30, 50, 100 µg/mL) on the viability of the glioblastoma cell line (U87MG) were studied after 24 h, 48 h, and 72 h. Our results indicated a time-dependent inhibitory effect on the viability of U87MG cells treated EBB. The main inhibitory effect of EBB was observed after 72 h; EBB treatment decreased cell viability to 49 -66%.

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Antitumour and pro-apoptotic actions of highly unsaturated fatty acids in glioma

Cited by 53 publications

References 26 publications

Protective role of glucose‐6‐phosphate dehydrogenase activity in the metabolic response of C6 rat glioma cells to polyunsaturated fatty acid exposure

Protective role of glucose‐6‐phosphate dehydrogenase activity in the metabolic response of C6 rat glioma cells to polyunsaturated fatty acid exposure

Microsomal prostaglandin E synthase-1 regulates human glioma cell growth via prostaglandin E2–dependent activation of type II protein kinase A

Chemical composition and antioxidant activity of beebread, and its influence on the glioblastoma cell line (U87MG)

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