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조승희,박미희,이희범,백명기,성하창,장희원,김주환,정헌상,한상배,홍진태 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.5
Ovarian cancer is a cancerous growth arisingfrom the ovary and with poor prognosis that usually haveresistant to all currently available treatments. Whether (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (butenal) synthesizedby Maillard reaction from fructose–tyrosine, has potentialtherapeutic activity against human ovarian cancer wasinvestigated using two ovarian cancer cell lines (PA-1, SKOV-3). We found that butenal could inhibit NF-jB/STAT3activity, thereby inducing apoptotic cell death of ovariancancer cells. We treated with several concentration ofbutenal each cell line differently (PA-1; 5, 10 and 15 lg/ml,SK-OV-3; 10, 20 and 30 lg/ml). First, ovarian cancer celllines exhibited constitutively active NF-jB, and treatmentwith butenal abolished this activation as indicated by DNAbinding activity. Second, butenal suppressed activation ofsignal transducer and activator of transcription-3 as indicatedby decreased phosphorylation and inhibition of Januskinase-2 phosphorylation. Third, butenal induced expressionof pro-apoptotic proteins such as proteolytic cleavageof PARP, Bax and activation of caspase-3, -8 and -9. Lastly, combination of butenal and TRAIL causesenhanced induction of apoptosis. Overall, our resultsindicate that butenal mediates its anti-proliferative andapoptotic effects through activation of multiple cell signalingpathways and enhances the TRAIL-induced apoptosis. These data suggested that butenal may be a potentialanti-cancer agent in ovarian cancer.