title: Anti-cancer effect of Cordyceps militaris in human colorectal carcinoma RKO cells via cell cycle arrest and mitochondrial apoptosis.
abstract: BACKGROUND
  Cordyceps militaris has been used as a traditional medicine in Asian countries for a long time. Different types of Cordyceps extract were reported to have various pharmacological activities including an anti-cancer effect. We investigated the inhibitory effect of Cordyceps militaris ethanol extract on a human colorectal cancer-derived cell line, RKO.
  
  
  METHODS
  RKO cells were treated with various concentrations of nucleosides-enriched ethanol extract of Cordyceps militaris for 48 h and cytotoxicity was measured using a CCK-8 assay. Then, xenograft Balb/c nude mice were injected with RKO cells and subsequently orally administered with ethanol extract of Cordyceps militaris every day for 3 weeks to examine the inhibitory effect on tumor growth. Lastly, the effect of Cordyceps militaris on cell cycle as well as apoptosis was measured using flow cytometry. Also, the expression of p53, caspase 9, cleaved caspase-3, cleaved PARP, Bim, Bax, Bak, and Bad were detected using western blot assay.
  
  
  RESULTS
  RKO cells were highly susceptible to the ethanol extract of Cordyceps militaris (CME) and the growth of RKO cells-derived tumor was significantly delayed by the treatment of Cordyceps militaris. Cordyceps militaris induced cell cycle arrest in G2/M phase (untreated; 20.5 %, CME 100 μg/ml; 61.67 %, CME 300 μg/ml; 66.33 %) and increased early apoptosis (untreated; 1.01 %, CME 100 μg/ml; 8.48 %, CME 300 μg/ml; 18.07 %). The expression of p53, cleaved caspase 9, cleaved caspase-3, cleaved PARP, Bim, Bak, and Bad were upregulated by the treatment of Cordyceps militaris.
  
  
  CONCLUSIONS
  Ethanol extract of Cordyceps militaris was highly cytotoxic to human colorectal carcinoma RKO cells and inhibited the growth of tumor in xenograft model. The anti-tumor effect of Cordyceps militaris was associated with an induction of cell cycle arrest and mitochondrial-mediated apoptosis.
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul, 132-714, Republic of Korea. oeo3oeo@gmail.com.|Innovative Drug Center, Duksung Women's University, Seoul, 132-714, Republic of Korea. oeo3oeo@gmail.com.
authors.forename: Hwan Hee
authors.initials: HH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul, 132-714, Republic of Korea. seulki1987@duksung.ac.kr.|Innovative Drug Center, Duksung Women's University, Seoul, 132-714, Republic of Korea. seulki1987@duksung.ac.kr.
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.affiliation: Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong, 369-873, Republic of Korea. agroup@korea.kr.
authors.forename: Kanghyo
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Medicinal Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong, 369-873, Republic of Korea. totoro69@korea.kr.
authors.forename: Yu Su
authors.initials: YS
authors.lastname: Shin
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences and Institute for Microorganisms, Kyungpook National University, Daegu, 702-701, Republic of Korea. hkang72@gmail.com.
authors.forename: Hyojeung
authors.initials: H
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul, 132-714, Republic of Korea. hyosun1102@gmail.com.|Innovative Drug Center, Duksung Women's University, Seoul, 132-714, Republic of Korea. hyosun1102@gmail.com.
authors.forename: Hyosun
authors.initials: H
authors.lastname: Cho
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045424:Complex Mixtures / Q000494:pharmacology / Q000627:therapeutic use*; D032661:Cordyceps; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D045424:Complex Mixtures