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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

Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira 228, Porto 4050-313, Portugal
Department of Biology, School of Sciences, University of Minho, Campus de Gualtar, Braga 4710-057, Portugal
Mountain Research Center (CIMO), ESA, Polytechnic Institute of Bragança, Apartado 1172, Bragança 5301-855, Portugal
Department of Plant Physiology, Institute for Biological Research "Siniša Stanković", University of Belgrade, 11000 Belgrade, Serbia
Plant Research International, Wageningen University and Research Centre, 6700AA Wageningen, The Netherlands
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology of the University of Porto, IPATIMUP, Rua Júlio Amaral de Carvalho, 45, Porto 4200-135, Portugal
Department of Pathology and Oncology, Faculty of Medicine, the University of Porto, Alameda Prof. Hernâni Monteiro, Porto 4200-319, Portugal
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Molecules 2015, 20(8), 13927-13940;
Received: 17 June 2015 / Revised: 16 July 2015 / Accepted: 27 July 2015 / Published: 31 July 2015
(This article belongs to the Collection Bioactive Compounds)
PDF [1270 KB, uploaded 31 July 2015]


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. View Full-Text
Keywords: Cordyceps militaris methanolic extract; p53; p21; cell cycle arrest; DNA damage Cordyceps militaris methanolic extract; p53; p21; cell cycle arrest; DNA damage

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Bizarro, A.; Ferreira, I.C.F.R.; Soković, M.; Van Griensven, L.J.L.D.; Sousa, D.; Vasconcelos, M.H.; Lima, R.T. 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. Molecules 2015, 20, 13927-13940.

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