Geranylgeranylacetone Induces Cyclooxygenase-2 Expression in Cultured Rat Gastric Epithelial Cells Through NF-κB

Nishida, Tsutomu; Yabe, Yuki; Fu, Haiying; Hayashi, Yujiro; Asahi, Kayoko; Eguchi, Hiroshi; Tsuji, S.; Tsujii, Masahiko; Hayashi, Norio

doi:10.1007/s10620-006-9661-8

Cited by 23 publications

(6 citation statements)

References 46 publications

(57 reference statements)

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“…Indeed, we previously administered a COX-2 inhibitor to mice with DSS-induced colitis and demonstrated that the presence of a COX-2 inhibitor during colitis exacerbated the colitis and did not show a preventive effect against colitis-induced tumorigenesis (13). Nishida et al evaluated the protective effect of GGA against noxious agents in rat gastric mucosa and demonstrated that GGA dose-dependently increased COX-2 expression and prostaglandin E2 production (24). In the present study, the administration of GGA suppressed iNOS expression and dose-dependently attenuated DSS-induced colitis.…”

Section: Discussionsupporting

confidence: 68%

Geranylgeranylacetone suppresses colitis-related mouse colon carcinogenesis

et al. 2015

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Section: Discussionsupporting

confidence: 68%

Geranylgeranylacetone suppresses colitis-related mouse colon carcinogenesis

et al. 2015

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“…NF-κB is a family of dimeric transcription factors that control the expression of numerous genes involved in cell growth, regulation of apoptosis, and neoplastic transformation (20,21). It was discovered in 1986 as a nuclear factor that binds to the enhancer region of the κB chain of immunoglobulin in B cells.…”

Section: Discussionmentioning

confidence: 99%

Curcumin reverses chemoresistance of human gastric cancer cells by downregulating the NF-κB transcription factor

Jing

Dai³

et al. 2011

Oncol Rep

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Abstract. Gastric cancer remains one of the major health problems worldwide. Chemotherapy is an important therapeutic modality for gastric cancer, but the success rate of this treatment is limited because of chemoresistance. The ubiquitously expressed transcription factor NF-κB has been suggested to be associated with chemoresistance of gastric cancer. Agents that can either enhance the effects of chemotherapeutics or overcome chemoresistance to chemotherapeutics are needed for the treatment of gastric cancer. Curcumin, a component of turmeric, is one such agent that has been shown to suppress NF-κB and increase the efficacy of chemotherapy. In this study, we investigated whether curcumin can reverse chemoresistance by downregulating NF-κB in human gastric cancer cells. SGC-7901 human gastric cancer cells was treated with chemotherapeutics (etoposide and doxorubicin) or by combined application of curcumin and chemotherapeutics. The viability of SGC-7901 cells was measured by MTT assay. Apoptosis of SGC-7901 cells was detected using the TUNEL and Annexin V/PI methods. The protein levels of NF-κB were analyzed by immunocytochemical staining. EMSA was used to confirm the increased nuclear translocation of RelA. The protein levels of p-IκBα, Bcl-2 and Bcl-xL were analyzed by Western blotting. The chemotherapeutics (etoposide and doxorubicin) suppressed the growth of SGC-7901 cells, in a time-dose-dependent manner. Use of curcumin in addition to these agents can suppress cell growth further (inhibitory rate: doxorubicin vs. doxorubicin + curcumin, 33% vs. 45%, p<0.05; etoposide vs. etoposide + curcumin, 35% vs. 48%, p<0.05). Furthermore, chemotherapeutics induced apoptosis of SGC-7901 cells and activated NF-κB. The combination of curcumin and chemotherapeutics induced apoptosis of SGC-7901 cells further, attenuated the activation of NF-κB, and reduced expression of the NF-κB-regulated anti-apoptotic gene products Bcl-2 and Bcl-xL. Curcumin potentiates the antitumor effects of chemotherapeutics in gastric cancer by suppressing NF-κB and NF-κB-regulated anti-apoptotic genes.

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“…More recently, Hashimoto et al [40] have reported that GGA inhibits cancer invasion and progression by attenuating Rho activation and Ras-mitogen-activated protein kinase (MAPK) in the mevalonate pathway. Nishida et al [41] reported that GGA induces COX-2 expression and increases PGE 2 production via activation of the nuclear factor-kappa B (NF-jB) sites on COX-2 gene promoters. Yenari et al [39] and Wojcik et al [42] reported that the mechanism by which the anti-inflammatory effects are exerted by GGA is through the inhibition of NF-jB activation.…”

Section: Discussionmentioning

confidence: 99%

Geranylgeranylacetone, a non-toxic inducer of heat shock protein, induces cell death in fibroblast-like synoviocytes from patients with rheumatoid arthritis

et al. 2009

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Fluvastatin (Fluv) is reported to induce apoptosis in rheumatoid arthritis (RA) synoviocytes through the blocking of protein geranylgeranylation. We report here our investigation of whether geranylgeranylacetone (GGA) induces cell death in RA synoviocytes. Synovial tissues were obtained from patients with RA at the time of total knee arthroplasty. Fibroblast-like synoviocytes (FLS) cultured in three passages were used for the experiments. The FLS were then cultured for 48 h in 48-well flat-bottomed plates containing various concentrations of GGA (0.1-4.0 microg/ml) and either 0.1 or 0.5 microM Fluv. We also examined the effect of GGA and Fluv in human fibroblasts from normal skin (CCD-25SK) and FLS from patients with osteoarthritis (OA). Cells demonstrating cell death were counted following trypan blue staining. In the absence of GGA, there was no apparent cell death, as evidence by trypan blue staining. Concentrations of GGA between 0.1 and 4.0 microg/ml induced cell death in RA FLS, but not in skin fibroblasts (CCD-25SK) nor OA FLS. The number of synoviocytes demonstrating cell death induced by 0.1 or 0.5 microM Fluv was significantly higher than that by the medium alone. In summary, we found that GGA induced cell death in RA FLS, suggesting that GGA may be a potential new therapeutic agent for RA as well as osteoporosis.

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Geranylgeranylacetone Induces Cyclooxygenase-2 Expression in Cultured Rat Gastric Epithelial Cells Through NF-κB

Cited by 23 publications

References 46 publications

Geranylgeranylacetone suppresses colitis-related mouse colon carcinogenesis

Geranylgeranylacetone suppresses colitis-related mouse colon carcinogenesis

Curcumin reverses chemoresistance of human gastric cancer cells by downregulating the NF-κB transcription factor

Geranylgeranylacetone, a non-toxic inducer of heat shock protein, induces cell death in fibroblast-like synoviocytes from patients with rheumatoid arthritis

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