Functional, molecular and pharmacological studies of p53 family proteins: from yeast to human cells

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Cordyceps militaris (L.) link fruiting body reduces NCI-H460 cellular viability through a mechanism involving p53 and p21

Publication . Bizarro, Ana; Ferreira, Isabel C.F.R.; Soković, Marina; Van Griensven, Leo J.L.D.; Sousa, Diana; Vasconcelos, M. Helena; Lima, Raquel T.

Mushroom extracts are recognized by their numerous potential medicinal properties. Recently, a methanolic extract from Cordyceps militaris (L.) Link (an edible entomopathogenic fungus widely used in traditional Chinese medicine) has been shown to inhibit cell growth of several human tumour cell lines [1,2]. However, its mechanism of action remained unknown. The aim of the present work was to study the antitumour mechanism of action of the methanolic extract of C. militaris, in the NCI-H460 cell line which is representative of non-small cell lung cancer. Results showed that the extract reduced viable cell number (observed with the trypan blue exclusion assay) by: i) decreasing cellular proliferation (analysed with the BrdU incorporation assay), ii) inducing cell cycle arrest at GO/GI phase (analysed by flow cytometry following propidium iodide-PI labelling) and iii) increasing apoptosis (analysed by flow cytometry following Annexin V-FITC and PI labelling). In addition, results also showed that treatment with the extract increased the cellular levels of p53 and p21. Moreover, this study also showed evidences of DNA damage caused by this extract, since an increase in the levels ofp-H2A.X and 53BP1 were observed, together with an increase in the number of 53BP1 foci/cell. In conclusion, this extract reduced NCI-H460 cellular viability, possibly through a mechanism which involves DNA damage and p53.

2014Conference object

Open access

Cordyceps militaris (L.) Link fruiting body reduces the growth of a non-small cell lung cancer cell line by increasing cellular levels of p53 and p21

Publication . Bizarro, Ana; Ferreira, Isabel C.F.R.; Soković, Marina; Van Griensven, Leo J.L.D.; Sousa, Diana; Vasconcelos, M. Helena; Lima, Raquel T.

Cordyceps militaris (L.) Link, an edible entomopathogenic fungus widely used in traditional Chinese medicine, has numerous potential medicinal properties including antitumor activity. The methanolic extract of C. militaris fruiting body was recently shown to have tumor cell growth inhibitory activity in several human tumor cell lines. Nonetheless, the mechanism of action involved is still not known. This work aimed at further studying the effect of the methanolic extract of C. militaris regarding its antitumor mechanism of action, using the non-small cell lung cancer cell line (NCI-H460) as a model. Results showed that treatment with the extract decreased cellular proliferation, induced cell cycle arrest at G0/G1 and increased apoptosis. In addition, the extract increased the levels of p53 and p21. Moreover, an increase in p-H2A.X and 53BP1 levels, together with an increase in the number of 53BP1 foci/cell (all indicative of DNA damage), were also observed after treatment with the extract. This work suggests that this extract affected NCI-H460 cellular viability through a mechanism involving DNA damage and p53 activation. This further supports the potential of this extract as a source of bioactive compounds, which may be used in anticancer strategies.

2015Journal article

Open access