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

Autor: Cho SH; College of Pharmacy, Medical Research Center, Chungbuk National University, 12, Gaeshin-dong, Heungduk-gu, Ch'ongju, 361-763, Chungbuk, Korea., Park MH, Lee HP, Back MK, Sung HC, Chang HW, Kim JH, Jeong HS, Han SB, Hong JT
Jazyk: angličtina
Zdroj: Archives of pharmacal research [Arch Pharm Res] 2014 May; Vol. 37 (5), pp. 652-61. Date of Electronic Publication: 2014 Jan 04.
DOI: 10.1007/s12272-013-0326-9
Abstrakt: 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.
Databáze: MEDLINE