title: Hexane/ethanol extract of Glycyrrhiza uralensis and its active compound isoangustone A induce G1 cycle arrest in DU145 human prostate and 4T1 murine mammary cancer cells.
abstract: Although licorice is known to exert anticarcinogenic effects, it contains large quantities of glycyrrhizin (GL), which causes severe hypertension. We have previously demonstrated that the hexane/ethanol extract of Glycyrrhiza uralensis (HEGU) contains no detectable GL and suppresses doxorubicin-induced apoptosis in H9c2 rat cardiac myoblasts. The principal objective of this study was to determine whether and by what mechanism HEGU and its active component, isoangustone A, inhibit cell-cycle progression in DU145 human prostate and 4T1 mouse breast cancer cells. HEGU and isoangustone A dose-dependently decreased DNA synthesis and induced G1 phase arrest in both DU145 and 4T1 cells. HEGU and isoangustone A reduced the levels of CDK2 and CDK4 as well as cyclin A and cyclin D1 proteins, and also induced a decrease in CDK2 activity. The addition of HEGU to drinking water significantly suppressed the orthotopic growth of 4T1 allografts and the expression of the proliferating nuclear cell antigen, CDK2 and CDK4 proteins in the tumor tissues. These results demonstrate the potential of HEGU containing isoangustone A as an antitumor agent.
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Republic of Korea.
authors.forename: Mi Ra
authors.initials: MR
authors.lastname: Seon
authors.forename: So Young
authors.initials: SY
authors.lastname: Park
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Kwon
authors.forename: Soon Sung
authors.initials: SS
authors.lastname: Lim
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Choi
authors.forename: Heesook
authors.initials: H
authors.lastname: Park
authors.forename: Do Young
authors.initials: DY
authors.lastname: Lim
authors.forename: Jong-Sang
authors.initials: JS
authors.lastname: Kim
authors.forename: Choong Hwan
authors.initials: CH
authors.lastname: Lee
authors.forename: Jongdai
authors.initials: J
authors.lastname: Kim
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005260:Female; D016193:G1 Phase / Q000187:drug effects*; D029882:Glycyrrhiza uralensis / Q000737:chemistry*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016213:Cyclins; D007529:Isoflavones; D010936:Plant Extracts; C551631:isoangustone A; C495894:CDK2 protein, human; C495900:CDK4 protein, human; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases