title: Involvement of p38 MAPK in the Anticancer Activity of Cultivated Cordyceps militaris.
abstract: Cordyceps militaris is a traditional Chinese medicine frequently used for tonic and therapeutic purposes. Reports from our laboratory and others have demonstrated that extracts of the cultivated fruiting bodies of C. militaris (CM) exhibit a potent cytotoxic effect against many cancer cell lines, especially human leukemia cells. Here, we further investigated the underlying mechanism through which CM is cytotoxic to cancer cells. The CM-mediated induction of PARP cleavage and its related DNA damage signal (γH2AX) was diminished by caspase inhibitor I. In contrast, a ROS scavenger failed to prevent CM-mediated leukemia cell death. Moreover, two signaling molecules, AKT and p38 MAPK, were activated during the course of apoptosis induction. Employing MTT analysis, we found that a p38 MAPK inhibitor but not an AKT inhibitor could rescue cells from CM-mediated cell death, as well as inhibit the cleavage of PARP, formation of apoptotic bodies and up-regulation of the γH2AX signal. These results suggest that CM-mediated leukemia cell death occurs through the activation of the p38 MAPK pathway, indicating its potential therapeutic effects against human leukemia.
authors.affiliation: Department and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
authors.forename: Shang-Min
authors.initials: SM
authors.lastname: Chou
authors.affiliation: Mucho Biotechnology Inc., Taipei 10684, Taiwan.
authors.forename: Wan-Jung
authors.initials: WJ
authors.lastname: Lai
authors.affiliation: Mucho Biotechnology Inc., Taipei 10684, Taiwan.|Department of Plant Pathology and Microbiology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Tzuwen
authors.initials: T
authors.lastname: Hong
authors.affiliation: Mucho Biotechnology Inc., Taipei 10684, Taiwan.
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Tsai
authors.affiliation: Mucho Biotechnology Inc., Taipei 10684, Taiwan.
authors.forename: Yen-Hsun
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Mucho Biotechnology Inc., Taipei 10684, Taiwan.
authors.forename: Cheng-Hsiang
authors.initials: CH
authors.lastname: Kao
authors.affiliation: Mucho Biotechnology Inc., Taipei 10684, Taiwan.
authors.forename: Richard
authors.initials: R
authors.lastname: Chu
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei 10617, Taiwan.|Center for Biotechnology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Tang-Long
authors.initials: TL
authors.lastname: Shen
authors.affiliation: Department and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.|Center for Biotechnology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Tsai-Kun
authors.initials: TK
authors.lastname: Li
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D032661:Cordyceps / Q000737:chemistry*; D004249:DNA Damage / Q000235:genetics; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D018922:HL-60 Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; C468783:H2AX protein, human; D006657:Histones; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Anti-Leukemia; Apoptosis; Cell Signaling; Cordyceps militaris; DNA Damage; p38 MAPK