Terrein induces apoptosis in HeLa human cervical carcinoma cells through p53 and ERK regulation
Terrein induces apoptosis in HeLa human cervical carcinoma cells through p53 and ERK regulation
复制标题
DOI：
10.3892/or.2013.2288
复制
发表时间：
2013-04-01
期刊：
影响因子：
4.2
通讯作者：
Wongsatayanon, Benjamas Thanomsub
中科院分区：
文献类型：
--
作者：
Porameesanaporn, Yuwarat;Uthaisang-Tanechpongtamb, Wanlaya;Wongsatayanon, Benjamas Thanomsub
Terrein是一种从土曲霉中提取的真菌代谢物，已被证明在人类细胞中具有多种生物活性，包括抑制黑素合成，以及抗炎、抗氧化和抗癌特性。在本研究中，Terrein被证明对HeLa人宫颈癌细胞具有显著的抗癌活性。Terrein对其他类型的癌细胞在相同范围内表现出增殖抑制，IC50为0.29 mm。诱导细胞死亡的生长抑制是通过细胞凋亡机制实现的。用脱氧核糖核酸特异性染料Hoechst 33342染色观察到染色质凝聚。流式细胞仪还检测到DNA片段化增加或亚GO峰。Terrein通过死亡受体和线粒体途径诱导细胞凋亡；caspase-3、-8和-9活性对特定的荧光底物有明显的切割作用。线粒体受损，表现为JC-1染色红绿比降低，Bax/Bcl2表达比升高。通过实时定量聚合酶链式反应进一步分析上游信号，发现p53、p21和ERK表达上调，表明它们在Terrein信号转导中的重要作用。这项研究首次表明Terrein通过调节P53和ERK诱导细胞凋亡来影响宫颈癌细胞的抗癌特性。我们的数据可能有助于扩大Terrein化合物的功能，也可能有助于发现新的抗癌药物。
Terrein, a fungal metabolite derived from Aspergillus terreus, has been shown to have a variety of biological activities in human cells including inhibition of melanogenesis, as well as anti-inflammatory, antioxidant and anticancer properties. In the present study, terrein was shown to have marked anticancer activity on HeLa human cervical carcinoma cells. Terrein exhibited inhibition of proliferation within the same ranges for other cancer cell types with an IC50 at 0.29 mM. The growth inhibition that induced cell death was via apoptosis mechanisms. Chromatin condensation was observed using the Hoechst 33342 stain, a DNA-specific dye. The increase of DNA fragmentation or the sub-GO peak was also detected by flow cytometry. The signaling used by terrein to induce apoptosis was via the death-receptor and mitochondrial pathways; the cleavage of specific fluorogenic substrates by caspase-3, -8 and -9 activities are clearly demonstrated. The mitochondria were damaged as demonstrated by the decrease of the red/green ratio of the JC-1 staining and the increase of the Bax/Bcl-2 expression ratio. Further analysis of the upstream signaling by the quantitative real-time polymerase chain reaction showed that p53, p21 and ERK were upregulated which indicates the importance of their roles on terrein signaling. This study is the first to show that terrein has an effect on the anticancer properties in cervical cancer cells by inducing apoptosis through p53 and ERK regulation. Our data may help expand the function of the terrein compound and may also aid in the discovery of new anticancer agents.