title: Inhibition of migration and invasion of LNCaP human prostate carcinoma             cells by cordycepin through inactivation of Akt.
abstract: Cordycepin (3'-deoxyadenosine), a major bioactive compound of Cordyceps             militaris, has many pharmacological actions, such as anti-inflammatory and anticancer             activities. In this study, the relationship between inhibition of cell motility             and anti-invasive activity by cordycepin in LNCaP human prostate carcinoma cells             was investigated. Within the concentration range that was not cytotoxic, cordycepin             time-dependently inhibited cell motility and invasiveness of LNCaP cells. The             inhibitory effects of cordycepin on cell invasiveness were associated with tightening             of tight junctions (TJs), which was demonstrated by an increase in transepithelial             electrical resistance (TER). Immunoblotting indicated that cordycepin decreases             levels of claudin proteins, which are major components of TJs that play a key             role in control and selectivity of paracellular transport. Furthermore, cordycepin             inhibited the expression and activity of matrix metalloproteinase (MMP)-2 and             MMP-9, and simultaneously increased levels of tissue inhibitor of metalloproteinase             (TIMP)-1 and TIMP-2. These effects were related to inactivation of the phosphoinositide             3-kinase (PI3K)/Akt pathway in LNCaP cells. These findings suggest that cordycepin             inhibits the migration and invasion of LNCaP cells by downregulating the activity             of TJs and MMPs, possibly in association with suppression of Akt activation.
authors.affiliation: Department of Biochemistry and Research Institute of Oriental                     Medicine, Dongeui University College of Oriental Medicine, Busan 614-052,                     Republic of Korea.
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Jeong
authors.forename: Cheng-Yun
authors.initials: CY
authors.lastname: Jin
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Han
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.forename: Chan Gil
authors.initials: CG
authors.lastname: Kim
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Jeong
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Jae-Dong
authors.initials: JD
authors.lastname: Lee
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D057167:Claudins / Q000378:metabolism; D003839:Deoxyadenosines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D057167:Claudins; D003839:Deoxyadenosines; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C058120:cordycepin