Department of Oral Microbiology, School of Dentistry, Kyungpook National University, Daegu 700-412, South Korea.
Cancer Lett. 2013 Feb 28;329(2):217-27. doi: 10.1016/j.canlet.2012.11.006. Epub 2012 Nov 23.
2'-Benzoyloxycinnamaldehyde (BCA) induces apoptosis in human cancer cells through ROS generation. BCA upregulates proapoptotic genes such as activating transcription factor 3 (ATF3), NSAID-activated gene 1 protein (NAG-1), and growth arrest and DNA-damage-inducible protein alpha (GADD45A) in prostate cancer cells. These genes are known to be induced by transcription factor early growth response protein 1 (EGR1). BCA induces significant EGR1 upregulation, while EGR1 knockdown decreases the induction of these genes with concurrent alleviation of cell death by BCA. Antioxidant glutathione pretreatment with BCA removes EGR1 expression increase, suggesting that EGR1 upregulation is dependent on oxidative stress generated by BCA. In prostate cancer cells, EGR1 localizes in the cytoplasm; however, BCA remarkably upregulates EGR1 nuclear translocalization, suggesting its possible effect as a transcriptional activator. BCA induces transient upregulation of importin-7 (IPO7) which is critical for EGR1 nuclear translocation, and IPO7 knockdown led to a significant decrease in chemosensitivity to BCA. Taken together, our findings suggest that BCA induces prostate cancer cell death via EGR1 upregulation and nuclear translocalization, followed by activation of proapoptotic target genes.
2'-苯甲酰氧基肉桂醛 (BCA) 通过产生 ROS 诱导人类癌细胞凋亡。BCA 上调前列腺癌细胞中促凋亡基因，如激活转录因子 3 (ATF3)、非甾体抗炎药激活基因 1 蛋白 (NAG-1) 和生长停滞和 DNA 损伤诱导蛋白 alpha (GADD45A)。这些基因已知由转录因子早期生长反应蛋白 1 (EGR1) 诱导。BCA 诱导 EGR1 显著上调，而 EGR1 敲低降低了这些基因的诱导，同时减轻了 BCA 引起的细胞死亡。BCA 预处理抗氧化剂谷胱甘肽去除 EGR1 表达增加，表明 EGR1 上调依赖于 BCA 产生的氧化应激。在前列腺癌细胞中，EGR1 定位于细胞质中；然而，BCA 显著上调 EGR1 核易位，表明其可能作为转录激活剂发挥作用。BCA 诱导进口蛋白 7 (IPO7) 的瞬时上调，这对于 EGR1 核易位至关重要，而 IPO7 敲低导致对 BCA 的化学敏感性显著降低。总之，我们的研究结果表明，BCA 通过 EGR1 上调和核易位诱导前列腺癌细胞死亡，随后激活促凋亡靶基因。
