title: Growth inhibition of U937 leukemia cells by aqueous extract of Cordyceps militaris through induction of apoptosis.
abstract: Cordyceps militaris is a traditional herbal ingredient, which has been used for patients suffering from cancer in Oriental medicine. In the present study, we investigated the biochemical mechanisms of anti-proliferative effects by aqueous extract of C. militaris (AECM) in human leukemia U937 cells. It was found that AECM could inhibit cell growth of U937 cells in a dose-dependent manner, which was associated with morphological change and apoptotic cell death such as formation of apoptotic bodies and DNA fragmentation. We observed the down-regulation of anti-apoptotic Bcl-2 expression and proteolytic activation of caspase-3 in AECM-treated U937 cells. However, AECM did not affect the pro-apoptotic Bax expression and activity of caspase-9. Furthermore, Western blotting and RT-PCR revealed that AECM treatment caused a dose-dependent inhibition of cyclooxygenase-2 and prostaglandin E2 accumulation. Taken together, these results indicated that the anti-proliferative effects of AECM were associated with the induction of apoptotic cell death through regulation of several major growth regulatory gene products such as Bcl-2 family expression and caspase protease activity, and AECM may have therapeutic potential in human leukemia treatment.
authors.affiliation: Department of Oriental Medicine, Dongeui University College of Oriental Medicine, Biomedical Research Center of Oriental Medicine, Busan 614-052, Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Hong
authors.forename: Jae-Yun
authors.initials: JY
authors.lastname: Lee
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Choi
authors.forename: Yong Tea
authors.initials: YT
authors.lastname: Lee
authors.forename: Dong Il
authors.initials: DI
authors.lastname: Park
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.forename: Yong-Kee
authors.initials: YK
authors.lastname: Jeong
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D032661:Cordyceps / Q000737:chemistry*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins; D010936:Plant Extracts / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020298:U937 Cells; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D008565:Membrane Proteins; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020169:Caspases; D015232:Dinoprostone