Does usnic acid affect microtubules in human cancer cells?

Abstract

Usnic acid, a lichen metabolite, is known to exert antimitotic and antiproliferative activities against normal and malignant human cells. Many chemotherapy agents exert their activities by blocking cell cycle progression, inducing cell death through apoptosis. Microtubules, protein structure involved in the segregation of chromosomes during mitosis, serve as chemotherapeutical targets due to their key role in cellular division as well as apoptosis. The aim of this work was to investigate whether usnic acid affects the formation and/or stabilisation of microtubules by visualising microtubules and determining mitotic indices after treatment. The breast cancer cell line MCF7 and the lung cancer cell line H1299 were treated with usnic acid 29 µM for 24 hours and two positive controls: vincristine (which prevents the formation of microtubules) or taxol (which stabilizes microtubules). Treatment of MCF7 and H1299 cells with usnic acid did not result in any morphological changes in microtubules or increase in the mitotic index. These results suggest that the antineoplastic activity of usnic acid is not related to alterations in the formation and/or stabilisation of microtubules.Keywords: usnic acid, microtubules, breast cancer, lung cancer. O ácido úsnico pode afetar microtúbulos em células cancerosas humanas?Resumo O ácido úsnico, um metabólito de liquens, é conhecido por sua atividade antimitótica e antiproliferativa em células humanas normais e malignas. Muitos quimioterápicos exercem suas atividades bloqueando a progressão do ciclo celular e induzindo morte celular por apoptose. Os microtúbulos, estruturas protéicas envolvidas na segregação dos cromossomos durante a mitose, servem como alvo quimioterapêutico devido ao seu importante papel tanto na divisão celular quanto nos mecanismos de morte celular por apoptose. O objetivo deste trabalho foi investigar se o ácido úsnico afeta a formação e/ou estabilização dos microtúbulos, a partir da visualização de microtúbulos e determinação de índices mitóticos após o tratamento. Células de câncer de mama MCF7 e de câncer de pulmão H1299 foram tratadas por 24 horas com 29 µM de ácido úsnico e dois controles positivos: vincristina (que impede a formação de microtúbulos) e taxol (que estabiliza microtúbulos). O tratamento das células MCF7 e H1299 com o ácido úsnico não resultou em aumento do índice mitótico. Os resultados sugerem que a atividade antineoplásica do ácido úsnico não está relacionada a alterações na formação e/ou estabilização de microtúbulos.Palavras-chave: ácido úsnico, microtúbulos, câncer de mama, câncer de pulmão.

Usnic acid biological activity: history, evaluation and usage

“…In was concluded that the antineoplastic activity of UA is not related to alterations in the formation and/or stabilization of microtubules. 27 The cytotoxic activity of purified lichen metabolites was evaluated by Brisdelli et al, in three human cancer cell lines included "MCF-7 (breast adenocarcinoma), HeLa (cervix adenocarcinoma) and HCT-116 (colon carcinoma)". 28 It was found that the highest cytotoxic activity against all cancer cell lines analyzed was higher than 25mM when compared with the other lichen.…”

Lichen Secondary Metabolites

“…A study on the effects of usnic acid on MCF-7 (estrogen dependent, wild-type p53) indicated no morphological changes in microtubules or increase in the mitotic index. This suggests that the antineoplastic activity of usnic acid is not related to alterations in the formation and/or stabilization of microtubules (O'Neill et al 2010).…”

Anticancer Activity of Lichen Metabolites and Their Mechanisms at the Molecular Level

“…Liu et al (2010) and Ren et al (2009) also identified a mitochondriamediated apoptosis pathway by showing changes in the ratio of Bax/Bcl-2 proteins after treatment with retigeric acid B or acetone extract of L. zahlbruckneri, respectively. At least for usnic acid, alterations in the formation and/or stabilization of microtubules are not responsible for the antimitotic and antiproliferative activities (O'Neill et al 2010). …”