KMID : 0043320140370050652
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Archives of Pharmacal Research 2014 Volume.37 No. 5 p.652 ~ p.661
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(E)-2,4-Bis(p-hydroxyphenyl)-2-butenal enhanced TRAIL-induced apoptosis in ovarian cancer cells through downregulation of NF-¥êB/STAT3 pathway
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Cho Seung-Hee
Park Mi-Hee Lee Hee-Peom Back Myong-Ki Sung Ha-Chang Chang Hee-Won Kim Joo-Hwan Jeong Heon-Sang Han Sang-Bae Hong Jin-Tae
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Abstract
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Ovarian cancer is a cancerous growth arising from the ovary and with poor prognosis that usually have resistant to all currently available treatments. Whether (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (butenal) synthesized by Maillard reaction from fructose?tyrosine, has potential therapeutic activity against human ovarian cancer was investigated using two ovarian cancer cell lines (PA-1, SK-OV-3). We found that butenal could inhibit NF-¥êB/STAT3 activity, thereby inducing apoptotic cell death of ovarian cancer cells. We treated with several concentration of butenal each cell line differently (PA-1; 5, 10 and 15 ¥ìg/ml, SK-OV-3; 10, 20 and 30 ¥ìg/ml). First, ovarian cancer cell lines exhibited constitutively active NF-¥êB, and treatment with butenal abolished this activation as indicated by DNA binding activity. Second, butenal suppressed activation of signal transducer and activator of transcription-3 as indicated by decreased phosphorylation and inhibition of Janus kinase-2 phosphorylation. Third, butenal induced expression of pro-apoptotic proteins such as proteolytic cleavage of PARP, Bax and activation of caspase-3, -8 and -9. Lastly, combination of butenal and TRAIL causes enhanced induction of apoptosis. Overall, our results indicate that butenal mediates its anti-proliferative and apoptotic effects through activation of multiple cell signaling pathways and enhances the TRAIL-induced apoptosis. These data suggested that butenal may be a potential anti-cancer agent in ovarian cancer.
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KEYWORD
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Ovarian cancer, NF-¥êB, STAT3, Akt, TRAIL
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