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(E)-2,4-Bis(p-hydroxyphenyl)-2-butenal enhanced TRAIL-induced apoptosis in ovarian cancer cells through downregulation of NF-κB/STAT3 pathway

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Abstract

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-κB/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 μg/ml, SK-OV-3; 10, 20 and 30 μg/ml). First, ovarian cancer cell lines exhibited constitutively active NF-κB, 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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Acknowledgments

This work was supported by the research grant of Chungbuk National University in 2011.

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Authors and Affiliations

  1. College of Pharmacy, Medical Research Center, Chungbuk National University, 12, Gaeshin-dong, Heungduk-gu, Ch’ongju, 361-763, Chungbuk, Korea

    Seung Hee Cho, Mi Hee Park, Hee Peom Lee, Myong Ki Back, Ha Chang Sung, Hee Won Chang, Sang Bae Han & Jin Tae Hong

  2. Agriculture, Life and Environments Sciences, Chungbuk National University, 12, Gaeshin-dong, Heungduk-gu, Ch’ongju, 361-763, Chungbuk, Korea

    Heon-Sang Jeong

  3. Osong Health Technology Administration Complex, 187 Osongsaengmyeong2(i)-ro, Osong- eup, Cheongwon-gun, 363-700, Chungbuk, Korea

    Joo Hwan Kim

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  1. Seung Hee Cho
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Correspondence to Jin Tae Hong.

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Cho, S.H., Park, M.H., Lee, H.P. et al. (E)-2,4-Bis(p-hydroxyphenyl)-2-butenal enhanced TRAIL-induced apoptosis in ovarian cancer cells through downregulation of NF-κB/STAT3 pathway. Arch. Pharm. Res. 37, 652–661 (2014). https://doi.org/10.1007/s12272-013-0326-9

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  • DOI: https://doi.org/10.1007/s12272-013-0326-9

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