Resveratrol inhibits glucose metabolism in human ovarian cancer cells

Kueck, Angela; Opipari, Anthony W.; Griffith, Kent A.; Tan, Lijun; Choi, Milheon; Huang, Jennifer T.; Wahl, Heather; Liu, J. Rebecca

doi:10.1016/j.ygyno.2007.07.065

Cited by 128 publications

(104 citation statements)

References 35 publications

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“…It has recently been shown that Res inhibits Akt/PKB and mTOR activation, two downstream kinases of class I PI3K, in ovarian cancer cells. 39 In line with these findings, we now report that Res inhibits the activation of Akt/PKB and mTOR in breast cancer cells. These data suggest that the non-canonical autophagy is triggered by mTOR inhibition in a manner similar to canonical autophagy.…”

Section: Discussionsupporting

confidence: 77%

Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells

et al. 2008

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Resveratrol, a polyphenol found in grapes and other fruit and vegetables, is a powerful chemopreventive and chemotherapeutic molecule potentially of interest for the treatment of breast cancer. The human breast cancer cell line MCF-7, which is devoid of caspase-3 activity, is refractory to apoptotic cell death after incubation with resveratrol. Here we show that resveratrol arrests cell proliferation, triggers death and decreases the number of colonies of cells that are sensitive to caspase-3-dependent apoptosis (MCF-7 casp-3 ) and also those that are unresponsive to it (MCF-7 vc ). We demonstrate that resveratrol (i) acts via multiple pathways to trigger cell death, (ii) induces caspase-dependent and caspase-independent cell death in MCF-7 casp-3 cells, (iii) induces only caspase-independent cell death in MCF-7 vc cells and (iv) stimulates macroautophagy. Using BECN1 and hVPS34 (human vacuolar protein sorting 34) small interfering RNAs, we demonstrate that resveratrol activates Beclin 1-independent autophagy in both cell lines, whereas cell death via this uncommon form of autophagy occurs only in MCF-7 vc cells. We also show that this variant form of autophagic cell death is blocked by the expression of caspase-3, but not by its enzymatic activity. In conclusion, this study reveals that non-canonical autophagy induced by resveratrol can act as a caspase-independent cell death mechanism in breast cancer cells.

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Section: Discussionsupporting

confidence: 77%

Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells

et al. 2008

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“…Resveratrol has been shown to inhibit both the growth and proliferation of human ovarian cancer cells, such as OVCAR-3, PA-1 and SKOV-3, through induction of apoptosis, DNA damage and S-phase arrest (Yang et al, 2003;Tyagi et al, 2005;Raj et al, 2008;Lee et al, 2009;Björklund et al, 2011;Lin et al, 2011;Marimuthu et al, 2011). Resveratrol induced cell death and growth inhibition in A1947, A2780, CaOV3, ES-2, SKOV3 and TOV112D cells by autophagocytosis and inhibition of glycolysis (Opipari et al, 2004;Kueck et al, 2007). Abrogation of HIF-1α and VEGF has been implicated in resveratrol-mediated inhibition of cell migration and angiogenesis in A2780/ CP80, CAOV-3 and ovcar-3 cells (Cao et al, 2004;Park et al, 2007).…”

Section: 1333 Resveratrol Effects On Ovarian Cancer Cells Differ In mentioning

confidence: 99%

Resveratrol Exerts Differential Effects in Vitro and in Vivo against Ovarian Cancer Cells

Stakleff¹,

Sloan²,

Blanco³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Epithelial ovarian cancer represents the most lethal gynecological cancer, and the high mortality rate makes this malignancy a major health concern. Poor prognosis results from an inability to detect ovarian cancers at an early, curable stage, as well as from the lack of an effective therapy. Thus, effective and novel strategies for prevention and treatment with non-toxic agents merit serious consideration. Resveratrol, obtained from grapes, berries, peanuts and red wine, has been shown to have a potent growth-inhibitory effect against various human cancer cells as well as in in vivo preclinical cancer models. The objective here was to evaluate potential antitumor effects of resveratrol in both in vitro and in vivo NuTu-19 ovarian cancer models. In vitro an invasion assay was performed. After 48 h, the numbers of viable cells that invaded the extracellular matrix layer were reduced by 94% with resveratrol in comparison to control. For the in vivo anti-tumor assessment, 10 rats were injected with NuTu-19 cells into the ovarian bursa. Thereafter, half were provided with a diet mixed with a dose of 100 mg resveratrol/kg body weight/day for 28 days. Following sacrifice, anticancer effects were assessed by histological evaluation of ovarian as well as surrounding tissues, and immunohistochemical detection of cell proliferation and apoptosis, but there were no observable differences between the control and resveratrol-treated groups for any of the biological endpoints. While resveratrol is effective in suppressing the in vitro cellular invasion of NuTu-19 ovarian cancer cells, these effects do not appear to impact on in vivo NuTu-19 ovarian cancers in rats.

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“…Building from what is known about this process, we postulate that glutamine metabolism may be inhibited through the scheme shown in Figure 6. Resveratrol has been shown to inhibit glucose uptake 62,63 leading to loss of p70S6K phosphorylation. 64,65 As glucose levels in the cell decline, glycosylation is inhibited and plasma membrane levels of growth factor receptors and transporters are reduced, 66 including the glutamine importer ASCT2.…”

Section: Discussionmentioning

confidence: 99%

A metabolic perturbation by U0126 identifies a role for glutamine in resveratrol-induced cell death

Freeman

Kim

Lisanti

et al. 2011

Cancer Biology & Therapy

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Recent evidence has identified substantial overlap between metabolic and oncogenic biochemical pathways, suggesting novel approaches to cancer intervention. For example, cholesterol lowering statins and the antidiabetes medication metformin both act as chemopreventive agents in prostate and other cancers. The natural compound resveratrol has similar properties: increasing insulin sensitivity, suppressing adipogenesis, and inducing apoptotic death of cancer cells in vitro. However, in vivo tumor xenografts acquire resistance to resveratrol by an unknown mechanism, while mouse models of metabolic disorders respond more consistently to the compound. Here we demonstrate that castrationresistant human prostate cancer C4-2 cells are more sensitive to resveratrol-induced apoptosis than isogenic androgendependent LNCaP cells. The MEK inhibitor U0126 antagonized resveratrol-induced apoptosis in C4-2 cells, but this effect was not seen with other MEK inhibitors. U0126 was found to inhibit mitochondrial function and shift cells to aerobic glycolysis independently of MEK. Mitochondrial activity of U0126 arose through decomposition, producing both mitochondrial fluorescence and cyanide, a known inhibitor of complex IV. Applying U0126 mitochondrial inhibition to C4-2 cell apoptosis, we tested the possibility that glutamine supplementation of citric acid cycle intermediate aketoglutarate may be involved. Suppression of the conversion of glutamate to a-ketoglutarate antagonized resveratrolinduced death in C4-2 cells. A similar effect was also seen by reducing extracellular glutamine concentration in the culture medium, suggesting that resveratrol-induced death is dependent on glutamine metabolism, a process frequently dysregulated in cancer. Further work on resveratrol and metabolism in cancer is warranted to ascertain if the glutamine dependence has clinical implications.

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Resveratrol inhibits glucose metabolism in human ovarian cancer cells

Cited by 128 publications

References 35 publications

Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells

Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells

Resveratrol Exerts Differential Effects in Vitro and in Vivo against Ovarian Cancer Cells

A metabolic perturbation by U0126 identifies a role for glutamine in resveratrol-induced cell death

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