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.
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.
Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira 228, Porto 4050-313, Portugal. sofiabizarro@gmail.com.|Department of Biology, School of Sciences, University of Minho, Campus de Gualtar, Braga 4710-057, Portugal. sofiabizarro@gmail.com.
Ana
A
Bizarro
Mountain Research Center (CIMO), ESA, Polytechnic Institute of Bragança, Apartado 1172, Bragança 5301-855, Portugal. iferreira@ipb.pt.
Isabel C F R
IC
Ferreira
Department of Plant Physiology, Institute for Biological Research "Siniša Stanković", University of Belgrade, 11000 Belgrade, Serbia. mris@ibiss.bg.ac.rs.
Marina
M
Soković
Plant Research International, Wageningen University and Research Centre, 6700AA Wageningen, The Netherlands. leo.vangriensven@wur.nl.
Leo J L D
LJ
van Griensven
Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira 228, Porto 4050-313, Portugal. dsousa@ipatimup.pt.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal. dsousa@ipatimup.pt.|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. dsousa@ipatimup.pt.
Diana
D
Sousa
Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira 228, Porto 4050-313, Portugal. hvasconcelos@ipatimup.pt.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal. hvasconcelos@ipatimup.pt.|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. hvasconcelos@ipatimup.pt.
M Helena
MH
Vasconcelos
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal. rlima@ipatimup.pt.|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. rlima@ipatimup.pt.|Department of Pathology and Oncology, Faculty of Medicine, the University of Porto, Alameda Prof. Hernâni Monteiro, Porto 4200-319, Portugal. rlima@ipatimup.pt.
Raquel T
RT
Lima
D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045424:Complex Mixtures / Q000494:pharmacology; D032661:Cordyceps / Q000737:chemistry*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage; D048690:Fruiting Bodies, Fungal / Q000737:chemistry*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000432:Methanol; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D045424:Complex Mixtures; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D000432:Methanol
Cordyceps militaris methanolic extract; DNA damage; cell cycle arrest; p21; p53