Celecoxib induces apoptosis in COX-2 deficient human gastric cancer cells through Akt/GSK3β/NAG-1 pathway

Pang, Rui‐Ping; Zhou, Jia‐Guo; Zeng, Zhirong; Li, Xiaoyan; Chen, Wei; Chen, Minhu; Hu, Pinjin

doi:10.1016/j.canlet.2006.11.032

Cited by 55 publications

(49 citation statements)

References 42 publications

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“…The reason why we were interested in studying NAG-1 as a molecular drug target was because of the previous reports that anticancer drugs could induce apoptosis by causing Akt dephosphorylation and glycogen synthase kinase (GSK) 3b activation, which eventually modulate NAG-1 upregulation-a proposed Akt/ GSK3b/NAG-1 pathway. 33,34 We had actually shown that AST treatment for 6-72 hr induces phospho-GSK3b overexpression in HT-29 cells time-dependently (Supporting Information Fig. 2), which is consistent with the upregulation of NAG-1.…”

Section: Discussionsupporting

confidence: 74%

A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID‐activated gene

Auyeung

Cho

2009

Intl Journal of Cancer

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Astragalus membranaceus has been used to ameliorate the side effects of antineoplastic drugs because of its immunomodulating nature. We had recently demonstrated that total Astragalus saponins (AST) possess anticarcinogenic and proapoptotic properties in human colon cancer cells and tumor xenograft. In this study, we identified NSAID-activated gene (NAG-1) as a potential molecular target of AST. The growth-inhibitory and proapoptotic effects of AST were assessed in a panel of human cancer cell lines. Hoechst 33342 nuclear staining, Annexin V-FITC/propidium iodide staining, Western immunoblotting, real-time PCR, luciferase reporter assay and electrophoretic mobility shift assay were conducted to determine the association of NAG-1 and related transcription factors with AST during its regulation of apoptotic activities. Moreover, the combined proapoptotic and NAG-1 promoting activities of AST and/or inhibitors of the PI3K-Akt pathway were also examined. AST caused overexpression of NAG-1, leading to PARP cleavage and apoptosis. The induction of NAG-1 promoter activity by the drug was associated with increased gene expression, in addition to prior increase in Egr-1 expression and DNA binding activity. AST-induced NAG-1 activation was intensified when PI3K inhibitor LY294002 or Akt inhibitor was cotreated and reversed by NAG-1 siRNA transfection. Nevertheless, the extent of NAG-1 induction could not be altered by the ERK inhibitor PD98059. Our results indicate that NAG-1 is a potential molecular target of AST in its antitumorigenic and proapoptotic actions, which would have additive effects when used along with PI3K-Akt inhibitors. The information obtained could facilitate future development of a novel target-specific chemotherapeutic agent with known molecular pathway. ' 2009 UICC

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Section: Discussionsupporting

confidence: 74%

A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID‐activated gene

Auyeung

Cho

2009

Intl Journal of Cancer

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“…For example, many dietary compounds associated with neoplastic cell growth suppression (Kim JS and colleagues, 2005 Lee SH and colleagues, 2005) induce MIC-1/GDF15 expression (36)(37)(38). Many studies have also suggested that MIC-1/GDF15 induces tumor apoptosis (11,39,40). However, in one study, MIC-1/GDF15 expression was associated with a more invasive gastric cancer cell line phenotype and could induce increased gastric cancer cell invasion in vitro.…”

Section: Discussionmentioning

confidence: 99%

Serum Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15): A Potential Screening Tool for the Prevention of Colon Cancer?

Brown

Hance

Rogers

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Macrophage inhibitory cytokine-1 (MIC-1/GDF15) mediates nonsteroidal anti-inflammatory drug (NSAID) protection from colonic polyps in mice and is linked to the development of colorectal carcinoma in humans. Therefore, changes in serum MIC-1/GDF15 levels could predict the presence of premalignant colonic polyposis and assist in population screening strategies.Methods: Serum MIC-1/GDF15 levels were measured in subjects in the Polyp Prevention Trial, in which NSAID use and colon cancer risk factors were defined. Subjects had an initial adenoma removed, a repeat colonoscopy removing previously unidentified polyps, and serum MIC-1/GDF15 estimation. Three years later recurrent adenomas were identified and serum MIC-1/GDF15 levels reestimated.

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“…Western blot analysis of ClC-3 expression was performed as we described previously [24]. Briefly, 50 µg of protein extracts from specific samples were separated by 8% SDS-PAGE and transferred to PVDF membranes (millipore).…”

Section: Western Blotmentioning

confidence: 99%

Static Pressure Promotes Rat Aortic Smooth Muscle Cell Proliferation via Upregulation of Volume-Regulated Chloride Channel

Qian

Pang

Zhu

et al. 2009

Cell Physiol Biochem

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Arterial smooth muscle cell proliferation is a key event in the development of hypertension associated vascular disease. Although previous studies have found that pressure itself can promote cell proliferation and DNA synthesis in vascular smooth muscle cells, the mechanisms are not clear. Recent accumulating evidence indicate that volume-regulated chloride channel plays an important role in the regulation of cell proliferation induced by numerous mitogenic factors. However, whether volume-regulated chloride channel is involved in hypertension-induced vascular smooth muscle cell proliferation remains to be determined. In this study, we found that static pressure promoted rat aortic smooth muscle cell proliferation and cell cycle progression. Static pressure treatment increased volume-regulated chloride currents and ClC-3 expression. Inhibition of chloride channel with pharmacological blockers or knockdown of ClC-3 with ClC-3 antisense transfection attenuated pressure-evoked cell proliferation and cell cycle progression. Static pressure enhanced the production of reactive oxygen species (ROS) in aortic smooth muscle cells. Diphenyleneiodonium (DPI) or apocynin pretreatment inhibited pressure-induced ROS production as well as cell proliferation. Furthermore, DPI or apocynin attenuated the pressure-induced upregulation of ClC-3 protein and hypoosmolarity-activated chloride current. Our data suggest that volume-regulated chloride channel plays a critical role in static pressure-induced cell proliferation and cell cycle progression, suggesting the therapeutic importance of volume-regulated chloride channel for treatment of hypertension attendant vascular complications.

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Celecoxib induces apoptosis in COX-2 deficient human gastric cancer cells through Akt/GSK3β/NAG-1 pathway

Cited by 55 publications

References 42 publications

A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID‐activated gene

A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID‐activated gene

Serum Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15): A Potential Screening Tool for the Prevention of Colon Cancer?

Static Pressure Promotes Rat Aortic Smooth Muscle Cell Proliferation via Upregulation of Volume-Regulated Chloride Channel

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