Usnic acid attenuates genomic instability in Chinese hamster ovary (CHO) cells as well as chemical-induced preneoplastic lesions in rat colon

ABSTRACT

Usnic acid (UA) is one of the pharmacologically most important compounds produced by several lichen species. To better understand the mechanism of action (MOA) of this important substance, this study examined the genotoxicity attributed to UA and its influence on mutagens with varying MOA using the micronucleus (MN) test in Chinese hamster ovary cells (CHO). Additional experiments were conducted to investigate the effect of UA on colon carcinogenesis in Wistar rats employing the aberrant crypt focus (ACF) assay. In vitro studies showed a significant increase in the frequency of MN in cultures treated with the highest UA concentration tested (87.13 µM). In contrast, UA concentrations of 10.89, 21.78, or 43.56 µM produced an approximate 60% reduction in chromosomal damage induced by doxorubicin, hydrogen peroxide, and etoposide, indicating an antigenotoxic effect. In the ACF assay, male Wistar rats treated with different UA doses (3.125, 12.5, or 50 mg/kg b.w.) and with the carcinogen 1,2-dimethylhydrazine exhibited a significantly lower incidence of neoplastic lesions in the colon than animals treated only with the carcinogen. Data suggest that the MOA responsible for the chemopreventive effect of UA may be related to interaction with DNA topoisomerase II and/or the antioxidant potential of the compound.

KEYWORDS:

• (+)-Usnic acid
• genotoxicity
• antigenotoxicity
• anticarcinogenic effect
• chemoprevention

Author Contributions

All authors participated in the design of the study, interpretation and analysis of the data, and revision of the manuscript. WR Cunha was responsible for the isolation of the chemical substance. MA Spanó and DC Tavares coordinated and supervised the study.

Conflict of interest

The authors declare no conflicts of interest.

Additional information

Funding

This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior: [Grant Number 001]; Fundação de Amparo ã Pesquisa do Estado de São Paulo: [Grant Number 307817/2015-6]; Conselho Nacional de Desenvolvimento Científico e Tecnológico: [Grant Number 307817/2015-6].