Usnic acid: a non-genotoxic compound with anti-cancer properties.
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.
Mayer
Margareth
M
Departamento de Morfologia e Fisiologia Animal, Universidade Federal de Pernambuco, Recife, PE, Brasil.
O'Neill
Mary A
MA
Murray
Karen E
KE
Santos-Magalhães
Nereide S
NS
Carneiro-Leão
Ana Maria A
AM
Thompson
Alastair M
AM
Appleyard
Virginia C L
VC
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001572:Benzofurans / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
D000970:Antineoplastic Agents; D001572:Benzofurans; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; C073339:usnic acid