ArticleOncogene2002
Novel target for induction of apoptosis by cyclo-oxygenase-2 inhibitor SC-236 through a protein kinase C-beta(1)-dependent pathway.
Article in Oncogene, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 73 citations in OpenAlex.
- Chemoprevention Against Gastric Cancer.Gastrointestinal endoscopy clinics of North America · 2021Review
- Establishment of highly tumorigenic human colorectal cancer cell line (CR4) with properties of putative cancer stem cells.PloS one · 2014Article
- Chronic psychological stress induces the accumulation of myeloid-derived suppressor cells in mice.PloS one · 2013Article
- COX-2/PGE2: molecular ambassadors of Kaposi's sarcoma-associated herpes virus oncoprotein-v-FLIP.Oncogenesis · 2012Article
- Article
- 12-O-tetradecanoylphorbol-1, 3-acetate induces the negative regulation of protein kinase B by protein kinase Calpha during gastric cancer cell apoptosis.Cellular & molecular biology letters · 2010Article
- Kaposi's sarcoma associated herpes virus (KSHV) induced COX-2: a key factor in latency, inflammation, angiogenesis, cell survival and invasion.PLoS pathogens · 2010Article
- Anti-apoptotic effects of protein kinase C-delta and c-fos in cisplatin-treated thyroid cells.British journal of pharmacology · 2009Article
- Protein kinase C-theta regulates KIT expression and proliferation in gastrointestinal stromal tumors.Oncogene · 2008Article
- Transcriptional activation of cyclooxygenase-2 by tumor suppressor p53 requires nuclear factor-kappaB.Oncogene · 2006Article
- Non-steroidal anti-inflammatory drugs in prevention of gastric cancer.World journal of gastroenterology · 2006Review
- Protein kinase C involvement in deoxycholate-induced apoptosis in human gastric cells.Digestive diseases and sciences · 2006Article
- Combination of celecoxib with percutaneous radiotherapy in patients with localised prostate cancer - a phase I study.Radiation oncology (London, England) · 2006Article
- 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole acts in a reactive oxygen species-dependent manner to suppress human lung cancer growth.Journal of cancer research and clinical oncology · 2006Article
- Celecoxib induces apoptosis in cervical cancer cells independent of cyclooxygenase using NF-kappaB as a possible target.Journal of cancer research and clinical oncology · 2004Article
- Article
- PPARgamma pathway activation results in apoptosis and COX-2 inhibition in HepG2 cells.World journal of gastroenterology · 2003Article
- Suppression of RelA/p65 nuclear translocation independent of IkappaB-alpha degradation by cyclooxygenase-2 inhibitor in gastric cancer.Oncogene · 2003Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of gastrointestinal cancers. Recently, a similar protective effect has been demonstrated by the specific cyclo-oxygenase-2 (COX-2) inhibitors. However, the exact mechanism that accounts for the anti-proliferative effect of specific COX-2 inhibitors is still not fully understood, and it is still controversial whether these protective effects are predominantly mediated through the inhibition of COX-2 activity and prostaglandin synthesis. Identification of molecular targets regulated by COX-2 inhibitors could lead to a better understanding of their pro-apoptotic and anti-neoplastic activities. In the present study, we investigated the effect and the possible molecular target of a COX-2-specific inhibitor SC-236 on gastric cancer. We showed that SC-236 induced apoptosis in gastric cancer cells. However, this effect was not dependent on COX-2 inhibition. SC-236 down-regulated the protein expression and kinase activity of PKC-beta(1), increased the expression of PKCdelta and PKCeta, but did not alter the expression of other PKC isoforms in AGS cells. Moreover, exogenous prostaglandins or PGE(2) receptor antagonists could not reverse the inhibition effect on PKCbeta(1) by SC-236, which suggested that this effect occurred through a mechanism independent of cyclo-oxygenase activity and prostaglandin synthesis. Overexpression of PKCbeta(1) attenuated the apoptotic response of AGS cells to SC-236 and was associated with overexpression of p21(waf1/cip1). Inhibition of PKCbeta(1)-mediated overexpression of p21(waf1/cip1) partially reduced the anti-apoptotic effect of PKCbeta(1). The down-regulation of PKCbeta(1) provides an explanation for COX-independent apoptotic effects of specific COX-2 inhibitor in cultured gastric cancer cells. We also suggest that PKCbeta(1) act as survival mediator in gastric cancer, and its down-regulation by COX-2 inhibitor SC-236 may provide new target for future treatment of gastric cancer.
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