Abstract

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.

Highlights

  • Cordyceps militaris (L.) Link, an edible Ascomycete, is an entomopathogenic fungus widely used in traditional Chinese medicine [1]

  • We have previously shown that a methanolic extract from C. militaris fruiting body could inhibit cell growth in human tumor cell lines and was not toxic to non-tumor liver porcine primary cells (PLP2) [16]

  • The present study aimed at gaining insight into the mechanism of action of the extract in a non-small cell lung cancer cell line (NCI-H460)

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Summary

Introduction

Cordyceps militaris (L.) Link, an edible Ascomycete, is an entomopathogenic fungus widely used in traditional Chinese medicine [1] It has been described as having numerous potent medicinal properties such as antitumor, anti-oxidant and anti-inflammatory [1,2]. Several studies, both in vitro as well as in human tumor xenografts in mice, refer to the antitumor activity of C. militaris [3,4]. A previous study from some of us has shown that a methanolic extract of C. militaris fruiting body presented activity as inhibitor of cell growth towards a panel of human tumor cell lines (while not affecting the proliferation of non-tumor porcine liver primary cells). To date, there is no information regarding the mechanism of action of this extract

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