Protein kinase C activation by PMA rapidly induces apoptosis through caspase-3/CPP32 and serine protease(s) in a gastric cancer cell line

Park, In-Chul; Park, Jong Bae; Rhee, Chang-Hun; Lee, Jong-Inn; Choe, Taeboo; Jang, Ja-Jun; Lee, Seung‐Hoon; Hong, Seok‐Il

doi:10.3892/ijo.18.5.1077

Cited by 14 publications

(16 citation statements)

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“…The multiplicity of effects of phorbol esters on biological systems is associated with the presence of phorbol esters receptors [10] and the types of phorbol esters. Fujii et al [10] and Park et al [11] reported the induction of apoptosis using phorbol esters in prostate cancer cells and gastric cancer cells.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, Fujii et al [10] reported that PMA induced apoptosis in prostate cancer cells through overexpression of PKCδ. Park et al [11] also concluded that the PMA induce apoptosis in gastric cancer cells through activation of PKC and the activation of serine protease(s) and caspase-3/CPP32. All these results indicate the potential of J. curcas plant as a source of bioactive compounds, but, the exact nature of the metabolite involved has to be elucidated, although it has been reported that phenolics, flavonoids, saponins and phorbol esters have been shown to be cytotoxic on different cell lines [9].…”

Section: Resultsmentioning

confidence: 99%

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Bioactive Compounds and Biological Activities of Jatropha curcas L. Kernel Meal Extract

Oskoueian

Abdullah

Ahmad

et al. 2011

IJMS

117

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Defatted Jatropha curcas L. (J. curcas) seed kernels contained a high percentage of crude protein (61.8%) and relatively little acid detergent fiber (4.8%) and neutral detergent fiber (9.7%). Spectrophotometric analysis of the methanolic extract showed the presence of phenolics, flavonoids and saponins with values of 3.9, 0.4 and 19.0 mg/g DM, respectively. High performance liquid chromatography (HPLC) analyses showed the presence of gallic acid and pyrogallol (phenolics), rutin and myricetin (flavonoids) and daidzein (isoflavonoid). The amount of phorbol esters in the methanolic extract estimated by HPLC was 3.0 ± 0.1 mg/g DM. Other metabolites detected by GC-MS include: 2-(hydroxymethyl)-2 nitro-1,3-propanediol, β-sitosterol, 2-furancarboxaldehyde, 5-(hydroxymethy) and acetic acid in the methanolic extract; 2-furancarboxaldehyde, 5-(hydroxymethy), acetic acid and furfural (2-furancarboxaldehyde) in the hot water extract. Methanolic and hot water extracts of kernel meal showed antimicrobial activity against both Gram positive and Gram negative pathogenic bacteria (inhibition range: 0–1.63 cm) at the concentrations of 1 and 1.5 mg/disc. Methanolic extract exhibited antioxidant activities that are higher than hot water extract and comparable to β-carotene. The extracts tended to scavenge the free radicals in the reduction of ferric ion (Fe3+) to ferrous ion (Fe2+). Cytotoxicity assay results indicated the potential of methanolic extract as a source of anticancer therapeutic agents toward breast cancer cells.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Bioactive Compounds and Biological Activities of Jatropha curcas L. Kernel Meal Extract

Oskoueian

Abdullah

Ahmad

et al. 2011

IJMS

117

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“…Our results suggest that LPS induces TNF-␣ secretion and apoptosis through a pathway that involves the activation of PKC. The activation of this kinase is sufficient to induce apoptosis in several cell types (22,47,55). By using two unrelated PKC inhibitors, we showed that PKC is also involved in the induction of apoptosis in macrophages by LPS.…”

Section: Discussionmentioning

confidence: 96%

PKCϵ is involved in JNK activation that mediates LPS-induced TNF-α, which induces apoptosis in macrophages

Comalada

Xaus²,

Valledor³

et al. 2003

American Journal of Physiology-Cell Physiology

104

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Lipopolysaccharide (LPS) is a powerful stimulator of macrophages and induces apoptosis in these cells. Using primary cultures of bone marrow-derived macrophages, we found that the autocrine production of tumor necrosis factor-alpha (TNF-alpha) has a major function in LPS-induced apoptosis. LPS activates PKC and regulates the different mitogen-activated protein kinases (MAPK). We aimed to determine its involvement either in the secretion of TNF-alpha or in the induction of apoptosis. Using specific inhibitors and mice with the gene for PKCepsilon disrupted, we found that LPS-induced TNF-alpha-dependent apoptosis is mostly mediated by PKCepsilon, which is not directly involved in the signaling mechanism of apoptosis but rather in the process of TNF-alpha secretion. In our cell model, all three MAPKs were involved in the regulation of TNF-alpha secretion, but at different levels. JNK mainly regulates TNF-alpha transcription and apoptosis, whereas ERK and p38 contribute to the regulation of TNF-alpha production, probably through posttranscriptional mechanisms. Only JNK activity is mediated by PKCepsilon in response to LPS and so plays a major role in TNF-alpha secretion and LPS-induced apoptosis. We demonstrated in macrophages that LPS involving PKCepsilon regulates JNK activity and produces TNF-alpha, which induces apoptosis.

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“…In contrast to gastric (46) and erythroleukemia (47) cancer cells, no caspase-3 cleavage was obtained in OVCAR-3 cells after PMA treatment (Supplementary Fig. S2).…”

Section: Resultsmentioning

confidence: 99%

Atypical Protein Kinase C ζ Exhibits a Proapoptotic Function in Ovarian Cancer

Nazarenko

Jenny

Keil

et al. 2010

Molecular Cancer Research

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Intracellular signaling governed by serine/threonine kinases comprises the molecular interface between cell surface receptors and the nuclear transcriptional machinery. The protein kinase C (PKC) family members are involved in the control of many signaling processes directing cell proliferation, motility, and survival. Here, we examined a role of different PKC isoenzymes in protein phosphatase 2A (PP2A) and HRSL3 tumor suppressordependent cell death induction in the ovarian carcinoma cell line OVCAR-3. Phosphorylation and activity of PKC isoenzymes were measured in response to PP2A or phosphoinositide 3-kinase inhibition or HRSL3 overexpression. These experiments indicated a regulation of PKCθ, ε, ζ, and ι through PP2A and/or HRSL3, but not of PKCα and β. Using isoform-specific peptide inhibitors and overexpression approaches, we verified a contribution to PP2A-and HRLS3-dependent apoptosis only for PKCζ, suggesting a proapoptotic function of this kinase. We observed a significant proportion of human ovarian carcinomas expressing high levels of PKCζ, which correlated with poor prognosis. Primary ovarian carcinoma cells isolated from patients also responded to okadaic acid treatment with increased phosphorylation of PKCζ and apoptosis induction. Thus, our data indicate a contribution of PKCζ in survival control in ovarian carcinoma cells and suggest that upregulation or activation of tyrosine kinase receptors in this tumor might impinge onto apoptosis control through the negative regulation of the atypical PKCζ. Mol Cancer Res; 8(6); 919-34. ©2010 AACR.

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Protein kinase C activation by PMA rapidly induces apoptosis through caspase-3/CPP32 and serine protease(s) in a gastric cancer cell line

Cited by 14 publications

References 0 publications

Bioactive Compounds and Biological Activities of Jatropha curcas L. Kernel Meal Extract

Bioactive Compounds and Biological Activities of Jatropha curcas L. Kernel Meal Extract

PKCϵ is involved in JNK activation that mediates LPS-induced TNF-α, which induces apoptosis in macrophages

Atypical Protein Kinase C ζ Exhibits a Proapoptotic Function in Ovarian Cancer

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