Mayer Margareth, O'Neill Mary A, Murray Karen E, Santos-Magalhães Nereide S, Carneiro-Leão Ana Maria A, Thompson Alastair M, Appleyard Virginia C L
Departamento de Morfologia e Fisiologia Animal, Universidade Federal de Pernambuco, Recife, PE, Brasil.
Anticancer Drugs. 2005 Sep;16(8):805-9. doi: 10.1097/01.cad.0000175588.09070.77.
The majority of human tumors bear inactive p53 or cellular factors that down-regulate the expression and activity of the p53 network. Therefore, finding therapies that are effective in such tumors is of great interest. Usnic acid, a normal component of lichens, showed activity against the wild-type p53 breast cancer cell line MCF7 as well as the non-functional p53 breast cancer cell line MDA-MB-231 and the lung cancer cell line H1299 (null for p53). In MCF7 cells treated with usnic acid, although there was an accumulation of p53 and p21 proteins, the transcriptional activity of p53 remained unaffected. We also found that there was no phosphorylation of p53 at Ser15 after treatment of MCF7 cells with usnic acid, suggesting that the oxidative stress and disruption of the normal metabolic processes of cells triggered by usnic acid does not involve DNA damage. The property of usnic acid as a non-genotoxic anti-cancer agent that works in a p53-independent manner makes it a potential candidate for novel cancer therapy.
大多数人类肿瘤携带无活性的p53或能下调p53网络表达和活性的细胞因子。因此，寻找对这类肿瘤有效的治疗方法备受关注。松萝酸是地衣的一种正常成分，对野生型p53乳腺癌细胞系MCF7、无功能p53乳腺癌细胞系MDA-MB-231以及肺癌细胞系H1299（p53缺失）均显示出活性。在用松萝酸处理的MCF7细胞中，尽管p53和p21蛋白有积累，但p53的转录活性未受影响。我们还发现，用松萝酸处理MCF7细胞后，p53在Ser15位点没有磷酸化，这表明松萝酸引发的细胞氧化应激和正常代谢过程的破坏不涉及DNA损伤。松萝酸作为一种以不依赖p53方式起作用的非基因毒性抗癌剂，使其成为新型癌症治疗的潜在候选药物。
