Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883, Republic of Korea.
Biochem Biophys Res Commun. 2011 Jun 10;409(3):489-93. doi: 10.1016/j.bbrc.2011.05.032. Epub 2011 May 12.
We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells.
我们利用从构巢曲霉中分离得到的抗生素asperlin 的生物学活性来对抗人宫颈癌细胞。我们发现 asperlin 能显著增加活性氧（ROS）的生成，同时显著降低细胞增殖。在用 asperlin 处理细胞后，还可以检测到 caspase-3 和 PARP 的裂解以及 Bcl-2 的减少。然而，抗氧化剂 N-乙酰-L-半胱氨酸（NAC）可以阻断 asperlin 的所有凋亡作用。ROS 和与 DNA 损伤相关的 G2/M 期阻滞和 ATM 磷酸化的增加支持了氧化应激参与 asperlin 诱导的细胞凋亡，此外，NAC 或 ATM 抑制剂 KU-55933 预处理可显著阻断细胞周期蛋白的表达和磷酸化以及对 asperlin 的 G2/M 期阻滞。总的来说，我们的研究首次证明，asperlin 可以通过在 HeLa 细胞中生成 ROS 来开发为一种潜在的抗癌治疗药物。
