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Pharmacology, Toxicology and Environmental Health

Apoptosis

Articles 1 - 3 of 3

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Multiple Mechanisms Are Involved In 6-Gingerol-Induced Cell Growth Arrest And Apoptosis In Human Colorectal Cancer Cells, Seong Lee, Maria Cekanova, Seung Baek Oct 2010

Multiple Mechanisms Are Involved In 6-Gingerol-Induced Cell Growth Arrest And Apoptosis In Human Colorectal Cancer Cells, Seong Lee, Maria Cekanova, Seung Baek

Maria Cekanova MS, RNDr, PhD

6-Gingerol, a natural product of ginger, has been known to possess anti-tumorigenic and pro-apoptotic activities. However, the mechanisms by which it prevents cancer are not well understood in human colorectal cancer. Cyclin D1 is a proto-oncogene that is overexpressed in many cancers and plays a role in cell proliferation through activation by beta-catenin signaling. Nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) is a cytokine associated with pro-apoptotic and anti-tumorigenic properties. In the present study, we examined whether 6-gingerol influences cyclin D1 and NAG-1 expression and determined the mechanisms by which 6-gingerol affects the growth of human colorectal cancer cells in ...


Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Expression Inhibits Urethane-Induced Pulmonary Tumorigenesis In Transgenic Mice, M Cekanova, S Lee, M Sukhthankar, R Donnell, T Eling, S Fischer, Seung Baek Dec 2008

Nonsteroidal Anti-Inflammatory Drug-Activated Gene-1 Expression Inhibits Urethane-Induced Pulmonary Tumorigenesis In Transgenic Mice, M Cekanova, S Lee, M Sukhthankar, R Donnell, T Eling, S Fischer, Seung Baek

Seung J Baek

The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) inhibits gastrointestinal tumorigenesis in NAG-1 transgenic mice (C57/BL6 background). In the present study, we investigated whether the NAG-1 protein would alter urethane-induced pulmonary lesions in NAG-1 transgenic mice on an FVB background (NAG-1(Tg+/FVB)). NAG-1(Tg+/FVB) mice had both decreased number and size of urethane-induced tumors, compared with control littermates (NAG-1(Tg+/FVB) = 16 +/- 4 per mouse versus control = 20 +/- 7 per mouse, P < 0.05). Urethane-induced pulmonary adenomas and adenocarcinomas were observed in control mice; however, only pulmonary adenomas were observed in NAG-1(Tg+/FVB) mice. Urethane-induced tumors from control littermates and NAG-1(Tg+/FVB) mice highly expressed proteins in the arachidonic acid pathway (cyclooxygenases 1/2, prostaglandin E synthase, and prostaglandin E(2) receptor) and highly activated several kinases (phospho-Raf-1 and phosphorylated extracellular signal-regulated kinase 1/2). However, only urethane-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation was decreased in NAG-1(Tg+/FVB) mice. Furthermore, significantly increased apoptosis in tumors of NAG-1(Tg+/FVB) mice compared with control mice was observed as assessed by caspase-3/7 activity. In addition, fewer inflammatory cells were observed in the lung tissue isolated from urethane-treated NAG-1(Tg+/FVB) mice compared with control mice. These results paralleled in vitro assays using human A549 pulmonary carcinoma cells. Less phosphorylated p38 MAPK was observed in cells overexpressing NAG-1 compared with control cells. Overall, our study revealed for the first time that the NAG-1 protein inhibits urethane-induced tumor formation, probably mediated by the p38 MAPK pathway, and is a possible new target for lung cancer chemoprevention


Ese-1/Egr-1 Pathway Plays A Role In Tolfenamic Acid-Induced Apoptosis In Colorectal Cancer Cells, Seong Lee, J Bahn, C Choi, Nichelle Whitlock, A English, S Safe, Seung Baek Nov 2008

Ese-1/Egr-1 Pathway Plays A Role In Tolfenamic Acid-Induced Apoptosis In Colorectal Cancer Cells, Seong Lee, J Bahn, C Choi, Nichelle Whitlock, A English, S Safe, Seung Baek

Seung J Baek

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to prevent colorectal tumorigenesis. Although antitumor effects of NSAIDs are mainly due to inhibition of cyclooxygenase activity, there is increasing evidence that cyclooxygenase-independent mechanisms may also play an important role. The early growth response-1 (EGR-1) gene is a member of the immediate-early gene family and has been identified as a tumor suppressor gene. Tolfenamic acid is a NSAID that exhibits anticancer activity in a pancreatic cancer model. In the present study, we investigated the anticancer activity of tolfenamic acid in human colorectal cancer cells. Tolfenamic acid treatment inhibited cell growth and induced apoptosis as ...