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KMID : 1161520150190060374
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Animal Cells and Systems
2015 Volume.19 No. 6 p.374 ~ p.384
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Prostaglandin E2 inhibits resveratrol-induced apoptosis through activation of survival signaling pathways in HCT-15 cell lines
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Islam Salman Ul
Shehzad Adeeb
Lee Young-Sup
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Abstract
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The COX-2 metabolite prostaglandin E2 (PGE2) promotes inflammation and progression of several cancers, including colon cancer. Resveratrol (3,5,4′-trihydroxy-trans-stilbene) induces apoptosis in cell lines and inhibits the invasion and metastasis of human colon cancer. PGE2 inhibits resveratrol-induced cell death; however, the underlying mechanisms are poorly understood. Therefore, the present study investigates the protection and survival effect of PGE2 against resveratrol-induced apoptosis in a human colorectal carcinoma (HCT-15) cell line. HCT-15 cells were treated with resveratrol and/or PGE2, and apoptotic cell death was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Resveratrol reduced HCT-15 cell viability and induced cell death through the production of ROS and the activation of caspase-3. Resveratrol treatment degraded poly (ADP-ribose) polymerase (PARP) in response to caspase-3 cleavage. Resveratrol treatment also decreased the activation of Ras-Raf-Erk and nuclear factor-κB (NF-κB) pathways and downregulated COX-2 expression, but did not regulate the secretion of extracellular PGE2. However, PGE2 exposure reversed resveratrol-induced oxidative stress and apoptosis, possibly through activation of the Ras-Raf-Erk pathway. PGE2 also positively regulated NF-κB activation and markedly increased the nuclear appearance of p50 and p65 subunits. Thus, this study provides insight into the mechanisms of resveratrol-induced apoptosis. Our results suggest that the inhibition of PGE2 and PGE2-induced activation of Ras-Raf-Erk and NF-κB signaling pathways may provide an alternative therapeutic strategy for the treatment and prevention of colon cancer.
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KEYWORD
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resveratrol, apoptosis, PGE2, colon cancer
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