Gao Peng, Zhai Fei, Guan Lei, Zheng Jie
Department of Pathology and Pathophysiology, School of Medical Science, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Oncol Lett. 2011 Jan;2(1):123-128. doi: 10.3892/ol.2010.205. Epub 2010 Nov 10.
Nordihydroguaiaretic acid (NDGA) and its derivatives possess anti-cancer effects on various types of cancer via the induction of apoptosis or cell cycle arrest. This study proved that NDGA inhibited cervical cancer SiHa cell growth and induced cell cycle arrest at the G(1) phase, which may be a consequence of cell cycle kinase inhibitor p21 induction. NDGA promoted acetylation of histone H3 in total and p21 gene-associated chromatin. This effect is gene selective, since NDGA has no impact on the p27 gene. NDGA also inhibited HPV-16 E6 gene transcription, which in turn resulted in the restoration of p53 protein levels. The silencing mediator for retinoid and thyroid hormone receptors (SMRT) is a key component of the HDAC3-HDAC4-N-CoR/SMRT complex. We found that NDGA significantly inhibited the transcription of SMRT, which, together with p53, may aid in the detection of the increase of histone H3 acetylation within the p21 gene. Our results suggest that NDGA induces p21 transcription by selectively elevating histone H3 acetylation associated with p21 gene and p53 protein levels via the inhibition of HPV-16 E6 expression.
去甲二氢愈创木酸（NDGA）及其衍生物通过诱导细胞凋亡或细胞周期停滞，对多种类型的癌症具有抗癌作用。本研究证明，NDGA抑制宫颈癌SiHa细胞生长，并诱导细胞周期停滞于G(1)期，这可能是细胞周期激酶抑制剂p21诱导的结果。NDGA促进了组蛋白H3的整体乙酰化以及与p21基因相关的染色质乙酰化。这种作用具有基因选择性，因为NDGA对p27基因没有影响。NDGA还抑制了HPV-16 E6基因的转录，进而导致p53蛋白水平的恢复。类视黄醇和甲状腺激素受体沉默介质（SMRT）是HDAC3-HDAC4-N-CoR/SMRT复合物的关键组成部分。我们发现，NDGA显著抑制SMRT的转录，这与p53一起，可能有助于检测p21基因内组蛋白H3乙酰化的增加。我们的结果表明，NDGA通过抑制HPV-16 E6表达，选择性地提高与p21基因相关的组蛋白H3乙酰化和p53蛋白水平，从而诱导p21转录。
