Induction of type 1 programmed cell death in U937 cells by the antioxidant, butylated hydroxy-toluene or the free radical spin trap, NTBN

Anderson, Karen K.; Ou, Dawei; Wu, Yu-Hauh; Jajeh, Ahmad; Harris, Jules E.

doi:10.1016/s0145-2126(99)00081-8

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…In contrast, DU145 and HPV7 cells had a very low amount of ROS. The introduction of v-ras into HPV7 cells moderately increased ROS production, which is consistent with others' findings that Ras is able to up-regulate ROS production (59,60). After treatment with GO6976, the amount of ROS in LNCaP or PC3 cells as well as in HPV7 cells expressing v-ras, was further increased.…”

Section: Down-regulation Of Pkc Causes the Accumulation Of Ros And Upsupporting

confidence: 90%

“…Furthermore, studies demonstrated that oncogenes can perturb the equilibrium of the intracellular redox state and cause DNA single strand breaks, which in turn disrupts genetic integrity (57). Despite regulating cell proliferation and transformation, the increase of ROS production has also been suggested to play an obligatory role in the induction of apoptosis by various apoptotic stimuli (59,60). In NFB-regulated programmed cell death, ROS accumulation precedes mitochondrial depolarization and caspase activation (65).…”

Section: Discussionmentioning

confidence: 99%

“…Studies have also shown that oncogenic Ras, under the condition of PKC abrogation, dramatically up-regulates ROS production that in turn participates in the apoptotic process (59,60). Because JNK1 expression and activity were not increased in LNCaP and PC3 cells and these cells were still susceptible to PKC suppression-induced apoptosis, it led us to test the redox state in these cells (Fig.…”

Section: Down-regulation Of Pkc Causes the Accumulation Of Ros And Upmentioning

confidence: 99%

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Modulation of Intracellular Signaling Pathways to Induce Apoptosis in Prostate Cancer Cells

Zhu

Xiao

Chen

2007

Journal of Biological Chemistry

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An understanding of the molecular pathways defining the susceptibility of prostate cancer, especially refractory prostate cancer, to apoptosis is the key for developing a cure for this disease. We previously demonstrated that up-regulating Ras signaling, together with suppression of protein kinase C (PKC), induces apoptosis. Dysregulation of various intracellular signaling pathways, including those governed by Ras, is the important element in the development of prostate cancer. In this study, we tested whether it is possible to modulate the activities of these pathways and induce an apoptotic crash among them in prostate cancer cells. Our data showed that DU145 cells express a high amount of JNK1 that is phosphorylated after endogenous PKC is suppressed, which initiates caspase 8 cleavage and cytochrome c release, leading to apoptosis. PC3 and LNCaP cells contain an activated Akt. The inhibition of PKC further augments Akt activity, which in turn induces ROS production and the accumulation of unfolded proteins in the endoplasmic reticulum, resulting in cell death. However, the concurrent activation of JNK1 and Akt, under the condition of PKC abrogation, dramatically augment the magnitude of apoptosis in the cells. Thus, our study suggests that Akt, JNK1, and PKC act in concert to signal the intracellular apoptotic machinery for a full execution of apoptosis in prostate cancer cells.It has been well documented that oncogenes (such as myc or ras) and their downstream effectors cannot only promote cell growth, but also, under certain circumstances, elicit programmed cell death or apoptosis (1-4). Mutational activation of the Ras gene is a key event in human cancer development (5-10). In the process of transformation, a persistent increase in Ras activity up-regulates its downstream effector pathways, leading to the phosphorylation and activation of pro-growth transcriptional factors (5-10). Despite its central involvement in cell growth and differentiation, we and others have demonstrated that treatment with PKC 2 inhibitors can induce apoptosis in various types of cells overexpressing oncogenic v-Ha or . In addition, stress-related kinases, such as c-Jun kinase (JNK)/p38 functions as Ras downstream effectors to initiate apoptosis (4).Ras governs multiple downstream effector pathways, such as Raf/MAP/ERK, PI3K/Akt, JNK/p38, and RalGSD (5-10). In response to mitogenic stimulation, Ras is activated, which in turn causes the plasma membrane translocation of the Raf/ MAPK/ERK cascade, resulting in phosphorylation of transcription factors and other proteins (17,18). The activation of PI3K or RalGDS has been suggested to be involved in the regulation of the rearrangement of cytoskeleton to promote growth-related signal transduction (19 -23). Furthermore, it has been demonstrated that in response to PKC inhibition, JNK1 acts as an intermediator to redirect Ras-mediated signaling for the initiation of caspase cascade (16). However, the suppression of JNK1 only partially blocked the apoptotic process, indicating that other ...

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Section: Down-regulation Of Pkc Causes the Accumulation Of Ros And Upsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Down-regulation Of Pkc Causes the Accumulation Of Ros And Upmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of Intracellular Signaling Pathways to Induce Apoptosis in Prostate Cancer Cells

Zhu

Xiao

Chen

2007

Journal of Biological Chemistry

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“…The lack of a protective effect of two other antioxidants, DTT and BHT, is not necessarily inconsistent with this conclusion. BHT and DTT react with ROS and protect against induction of apoptosis in some cell systems [41,63] but exert proapoptotic and prooxidant effects in other systems [64,65]. Our results show that both of these agents are proapoptotic in preovulatory follicles.…”

Section: Dmba Induces Apoptosis In Preovulatory Folliclesmentioning

confidence: 64%

Induction of Apoptosis by 9,10-Dimethyl-1,2-Benzanthracene in Cultured Preovulatory Rat Follicles Is Preceded by a Rise in Reactive Oxygen Species and Is Prevented by Glutathione1

Tsai-Turton

Nakamura

Luderer

2007

Biology of Reproduction

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The polycyclic aromatic hydrocarbon (PAH) 9,10-dimethyl-1,2-benzanthracene (DMBA) destroys primordial, primary, and secondary ovarian follicles in rodents, but its effects on antral follicles have received limited attention. PAHs are metabolized to reactive species, some of which can undergo redox cycling to generate reactive oxygen species (ROS). We previously showed that ROS initiate apoptosis in preovulatory follicles cultured without gonadotropin support and that glutathione (GSH) depletion induces apoptosis in the presence of gonadotropins. In the present study, we tested the hypothesis that DMBA induces apoptosis in preovulatory follicles, which is mediated by ROS and prevented by GSH. Preovulatory follicles were isolated from ovaries of 25-day-old rats 48 h after the injection of 10 IU of eCG and were cultured with DMBA in the presence of FSH for 2 to 48 h. DMBA induced granulosa cell (GC) and theca cell (TC) apoptosis at 48 h, as judged by TUNEL and activated caspase-3 immunostaining. DMBA treatment also increased the numbers of GCs and TCs that immunostained for the proapoptotic protein BAX. Follicular ROS levels were significantly increased in DMBA-treated follicles at 12, 24, and 48 h. GSH supplementation protected against and GSH depletion enhanced the induction of apoptosis in GCs and TCs by DMBA. These findings suggest that GSH is a critical protective mechanism against DMBA-induced apoptosis in antral follicles and that ROS generation may mediate DMBA-induced GC apoptosis.

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“…Studies also demonstrated that oncogenes perturb the equilibrium of intracellular redox state and cause DNA single strand breaks, which in turn disrupted genetic integrity (39). Despite regulating cell proliferation and transformation, the increase of ROS production was also shown to play an obligatory role in the induction of apoptosis induced by various apoptotic stimuli (40). In NF κB-regulated programmed cell death, ROS accumulation precedes mitochondrial depolarization and caspase activation (41).…”

Section: Discussionmentioning

confidence: 99%

Differential Sensitization of Different Prostate Cancer Cells to Apoptosis

et al. 2010

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Although protein kinase C (PKC) plays an important role in sensitizing prostate cancer cells to apoptosis and suppression of PKC is able to trigger an apoptotic crisis in cells harboring oncogenic ras, little is known about whether dyregulation of Ras effectors in prostate cancer cells, together with loss of PKC are synthetically lethal. The current study aims at investigating whether prostate cancer cells with aberrant Ras effector signaling are sensitive to the treatment with HMG (a PKC inhibitor) for the induction of apoptosis. We show that prostate cancer DU145 cells express a high level of JNK1 become susceptible to apoptosis after the treatment with HMG, in which caspase 8 is activated and cytochrome c is released to the cytosol. In contrast, the addition of HMG sensitizes LNCaP or PC3 prostate cancer cells harboring an active Akt to apoptosis, in which ROS is upregulated to induce the UPR and GADD153 expression. The concurrent activation of JNK1 and Akt has an additive effect on apoptosis following PKC suppression. Thus, the data identify Akt and JNK1 as potential targets in prostate cancer cells for PKC inhibition-induced apoptosis.

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Induction of type 1 programmed cell death in U937 cells by the antioxidant, butylated hydroxy-toluene or the free radical spin trap, NTBN

Cited by 9 publications

References 33 publications

Modulation of Intracellular Signaling Pathways to Induce Apoptosis in Prostate Cancer Cells

Modulation of Intracellular Signaling Pathways to Induce Apoptosis in Prostate Cancer Cells

Induction of Apoptosis by 9,10-Dimethyl-1,2-Benzanthracene in Cultured Preovulatory Rat Follicles Is Preceded by a Rise in Reactive Oxygen Species and Is Prevented by Glutathione1

Differential Sensitization of Different Prostate Cancer Cells to Apoptosis

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