title: Synergistic property of cordycepin in cultivated Cordyceps militaris-mediated apoptosis in human leukemia cells.
abstract: Cordyceps militaris is a well-known Chinese traditional medicinal mushroom frequently used for tonics and recently of a potential interest for cancer intervention. Here, we explored the cancer cell killing activity of the hot water extracts of C. militaris cultured mycelia (CM(MY)) and cultivated fruiting bodies (CM(FB)). We found that CM(FB) exhibited a greater cytotoxic effect against various cancer cells over CM(MY). Apoptotic phenotypes including apoptotic body formation, DNA laddering, caspase 3 activation and cleavage of PARP proteins were induced by CM(FB) treatment but only slightly induced by same concentration of CM(MY) treatment in human HL-60 leukemia cells. Cordycepin in CM(FB) (10.47 mg/g) is significantly higher (∼ 15.2 times) than that of CM(MY) (0.69 mg/g). Using isobolographic analysis, the synergy of cytotoxicity was observed across different combined concentrations of CM(MY) and cordycepin. By complementing cordycepin into CM(MY) to the level comparable with CM(FB), we observed that CM(MY) (500 μg/ml) with cordycepin (4.8 μg/ml) induced apoptosis to a level similar to that induced by CM(FB) (500 μg/ml). Together, our results suggest that cordycepin possesses a synergistic cytotoxic effect with Cordyceps militaris-mediated apoptosis in human leukemia cells and therefore explaining a better anti-proliferating activity of CM(FB) over CM(MY).
authors.affiliation: Department and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Shang-Min
authors.initials: SM
authors.lastname: Chou
authors.affiliation: Mucho Biotechnology Inc., Taipei 106, Taiwan.
authors.forename: Wan-Jung
authors.initials: WJ
authors.lastname: Lai
authors.affiliation: Mucho Biotechnology Inc., Taipei 106, Taiwan; Department of Plant Pathology and Microbiology, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Tzu-Wen
authors.initials: TW
authors.lastname: Hong
authors.affiliation: Mucho Biotechnology Inc., Taipei 106, Taiwan.
authors.forename: Jui-Ya
authors.initials: JY
authors.lastname: Lai
authors.affiliation: Mucho Biotechnology Inc., Taipei 106, Taiwan.
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Tsai
authors.affiliation: Mucho Biotechnology Inc., Taipei 106, Taiwan.
authors.forename: Yen-Hsun
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Mucho Biotechnology Inc., Taipei 106, Taiwan.
authors.forename: Sz-Hsien
authors.initials: SH
authors.lastname: Yu
authors.affiliation: Mucho Biotechnology Inc., Taipei 106, Taiwan.
authors.forename: Cheng-Hsiang
authors.initials: CH
authors.lastname: Kao
authors.affiliation: Mucho Biotechnology Inc., Taipei 106, Taiwan.
authors.forename: Richard
authors.initials: R
authors.lastname: Chu
authors.affiliation: Department of Animal Science and Technology, National Taiwan University, Taipei 106, Taiwan; Center for Biotechnology, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Shih-Torng
authors.initials: ST
authors.lastname: Ding
authors.affiliation: Department and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan; Center for Biotechnology, National Taiwan University, Taipei 106, Taiwan. Electronic address: tsaikunli@ntu.edu.tw.
authors.forename: Tsai-Kun
authors.initials: TK
authors.lastname: Li
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei 106, Taiwan; Center for Biotechnology, National Taiwan University, Taipei 106, Taiwan. Electronic address: shentl@ntu.edu.tw.
authors.forename: Tang-Long
authors.initials: TL
authors.lastname: Shen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D032661:Cordyceps / Q000737:chemistry*; D003839:Deoxyadenosines / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D003839:Deoxyadenosines; C058120:cordycepin
keywords: Apoptosis; Cancer-cell killing; Cordycepin; Cordyceps militaris; Leukemia; Synergistic