Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells
Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells
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DOI：
10.1016/j.bbrc.2012.11.018
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发表时间：
2013-01-04
影响因子：
3.1
通讯作者：
Lee, Seong-Ho
中科院分区：
文献类型：
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作者：
Jeong, Jin Boo;Lee, Seong-Ho
原儿茶醛（PCA）是一种天然存在的多酚，存在于大麦、绿色卡文迪什香蕉和葡萄藤叶中。虽然有几项研究报告了五氯苯甲醚在乳腺癌和白血病细胞中的生长抑制活性，但其潜在机制仍然知之甚少。因此，我们进行了体外研究，以调查PCA的治疗是否影响人结直肠癌细胞的细胞增殖和凋亡，并确定PCA介导癌细胞生长停滞和凋亡的潜在机制。暴露于人结肠直肠癌细胞（HCT 116和SW 480细胞）的PCA抑制细胞生长，并以剂量依赖性方式诱导凋亡。PCA在蛋白和mRNA水平上降低cyclin D1的表达，抑制cyclin D1启动子的荧光素酶活性，表明PCA下调cyclin D1基因的转录。我们还观察到PCA处理减弱了组蛋白去乙酰化酶（HDAC）的酶活性，并降低了HDAC 2的表达，但没有HDAC 1。这些发现表明，PCA的细胞生长抑制和凋亡可能是HDAC2介导的细胞周期蛋白D1抑制的结果。(C)2012 Elsevier Inc. All rights reserved.
Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment of PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression. (C) 2012 Elsevier Inc. All rights reserved.