Role of PKC-δ activity in glutathione-depleted neuroblastoma cells

Domenicotti, Cinzia; Marengo, Barbara; Verzola, Daniela; Garibotto, Giacomo; Traverso, Nicola; Patriarca, Stefania; Maloberti, Giuseppe; Cottalasso, Damiano; Poli, Giuseppe; Passalacqua, Mario; Melloni, Edon; Pronzato, Maria Adelaide; Marinari, Umberto M.

doi:10.1016/s0891-5849(03)00332-0

Cited by 49 publications

(35 citation statements)

References 50 publications

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“…Thus, in the present study, it is conceivable that the ROS induced by curcumin may have mediated the activation or phosphorylation of PTK, but also PDK1 and PKCδ (although not EGFR, data not shown), by promoting oxidation of critical cysteine residues in these enzymes. Our finding regarding PKCδ, which has cysteine-rich motifs in its regulatory domain that are particularly susceptible to oxidation [Gopalakrishna and Anderson, 1989], is in harmony with the observation that BSO-induced depletion of glutathione and consequent stimulation of ROS production in neuroblastoma cells was associated with activation of PKCδ [Domenicotti et al, 2003b]. It is possible, however, that the ROS generated as a result of exposing HCT-116 cells to curcumin may not be the only mechanism of PKCδ activation.…”

Section: Discussionsupporting

confidence: 87%

“…Upon activation, PKCδ is known to undergo translocation, such as to the mitochondria in glutathione-depleted neuroblastoma cells [Domenicotti et al, 2003b] and in H 2 O 2 -treated myeloid leukemia cells [Majumder et al, 2001]. To determine if curcumin caused a similar mitochondrial translocation but in HCT116 cells, the distribution of phospho-PKCδ was evaluated.…”

Section: Curcumin-induced Activation Of Pkcδ Via Pi3k and Localizatiomentioning

confidence: 99%

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Curcumin‐induced GADD153 upregulation: Modulation by glutathione

Scott¹,

Loo²

2006

J of Cellular Biochemistry

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Abstract:As we reported previously, GADD153 is upregulated in colon cancer cells exposed to curcumin. In the present study, we ascertained the involvement of glutathione and certain sulfhydryl enzymes associated with signal transduction in mediating the effect of curcumin on GADD153. Curcumin-induced GADD153 gene upregulation was attenuated by reduced glutathione (GSH) or N-acetylcysteine (NAC) and potentiated by the glutathione synthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO). Additionally, GSH and NAC decreased the intracellular content of curcumin. Conversely, curcumin decreased intracellular glutathione and also increased the formation of reactive oxygen species (ROS) in cells, but either GSH or NAC prevented both of these effects of curcumin. In affecting the thiol redox status, curcumin caused activation of certain sulfhydryl enzymes involved in signal transduction linked to GADD153 expression. Curcumin increased the expression of the phosphorylated forms of PTK, PDK1, and PKC-δ, which was attenuated by either GSH or NAC and potentiated by BSO. Furthermore, selective inhibitors of PI3K and PKC-δ attenuated curcumin-induced GADD153 upregulation. Collectively, these findings suggest that a regulatory thiol redox-sensitive signaling cascade exists in the molecular pathway leading to induction of GADD153 expression as caused by curcumin.

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Section: Discussionsupporting

confidence: 87%

Section: Curcumin-induced Activation Of Pkcδ Via Pi3k and Localizatiomentioning

confidence: 99%

Curcumin‐induced GADD153 upregulation: Modulation by glutathione

Scott¹,

Loo²

2006

J of Cellular Biochemistry

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“…Our previous reports have demonstrated that the apoptotic process of human NB cells is strictly related to intracellular ROS overproduction (44) and also in this context, we have found that a 2.5-fold increase of ROS levels was accompanied by the appearance of apoptotic features in LAN5 cells treated with 20 ppm of A. oroides.…”

Section: Discussionsupporting

confidence: 61%

Effects of Agelas oroides and Petrosia ficiformis crude extracts on human neuroblastoma cell survival

Ferretti

Marengo²,

Ciucis³

et al. 2007

Int J Oncol

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Abstract. Among marine sessile organisms, sponges (Porifera) are the major producers of bioactive secondary metabolites that defend them against predators and competitors and are used to interfere with the pathogenesis of many human diseases. Some of these biological active metabolites are able to influence cell survival and death, modifying the activity of several enzymes involved in these cellular processes. These natural compounds show a potential anticancer activity but the mechanism of this action is largely unknown. In this study, we investigated the effects of two Mediterranean sponges, Agelas oroides and Petrosia ficiformis on the viability of human neuroblastoma cells. Upon treatment with the methanolic extract of Petrosia ficiformis, a marked cytotoxic effect was observed at any concentration or time of exposure. In contrast, a time-and dose-dependent effect was monitored for Agelas oroides that induced the development of apoptotic features and ROS production in LAN5 cells. These events were suppressed by calpeptin or zVAD and by vitamin C suggesting that the cell death caused by Agelas oroides was calpain-and caspasedependent and of oxidative nature. Comet assay showed that this methanolic extract was not able to produce a genotoxic effect. Future studies will be applied to investigate the effect of isolated bioactive compounds from crude extract of this sponge which are potentially useful for cancer therapeutics.

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“…1). It has previously been reported that ascorbate induces cell death via PKCδ pathway in neuroblastoma cells (27), the Ca 2+ signal in human hepatoma cells (28), glioblastoma cells, renal carcinoma cells (29), and the caspase-dependent pathway in melanoma cells (30). Based on these studies, we examined the effect of some chemical inhibitors, such as rottlerin, a PKCδ specific inhibitor, nifedipine, a Ca 2+ signal blocker, a pancaspase inhibitor, and MG132, an AIF blocker (19), on ascorbate-induced cell death.…”

Section: Discussionmentioning

confidence: 99%

Ascorbate (vitamin C) induces cell death through the apoptosis-inducing factor in human breast cancer cells

et al. 2007

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Abstract. Although ascorbate (Vitamin C) has been shown to inhibit cell growth and induce cell death in variety of cancer cells, results reported in other studies are inconsistent with this conclusion. It was previously reported that ascorbate induces apoptosis in human breast cancer cells. However, the molecular mechanism for this is not clear. In this study, we demonstrate that ascorbate induces cell death through the apoptosis-inducing factor (AIF) in the human breast cancer cell lines, SK-BR3 and Hs578T, but not in a normal breast cell line, Hs578. Ascorbate treatment caused the nuclear translocation of AIF, which is retained in the mitochondria in healthy cells, but caspase cleavage is not induced. Moreover, MG132, an inhibitor of AIF release from mitochondria, blocked the induction of cell death. Furthermore, cells that had been treated with human AIF-specific siRNA resisted cell death induced by ascorbate, implying that the translocation of AIF from mitochondria to the nucleus is responsible for ascorbate-mediated cell death. Therefore, these results suggest that ascorbate activates a caspase-independent and AIFmediated cell death pathway in human breast cancer cells, SK-BR3, and Hs578T.

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Role of PKC-δ activity in glutathione-depleted neuroblastoma cells

Cited by 49 publications

References 50 publications

Curcumin‐induced GADD153 upregulation: Modulation by glutathione

Curcumin‐induced GADD153 upregulation: Modulation by glutathione

Effects of Agelas oroides and Petrosia ficiformis crude extracts on human neuroblastoma cell survival

Ascorbate (vitamin C) induces cell death through the apoptosis-inducing factor in human breast cancer cells

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