title: A novel anticancer agent, icaritin, induced cell growth inhibition, G1 arrest and mitochondrial transmembrane potential drop in human prostate carcinoma PC-3 cells.
abstract: Icariin and icaritin with prenyl group have been demonstrated for their selective estrogen receptor modulating activities. We screened their effects on cell growth in human prostate carcinoma PC-3 cell line (estrogen receptor positive) in vitro. PC-3 cell line was used for the measurement of anti-carcinoma activities of 0-100 micromol/l icaritin and 30 micromol/l icariin. 1 micromol/l 17-beta estradiol (E(2)) served as the estrogen positive control, and 1 micromol/l ICI 182,780 [7 alpha-[9 (4,4,5,5,5-pentafluoropentyl) sulfinyl] nonyl]-estra-1,3,5(10)-triene-3,17h-diol]] served as the specific estrogen receptor antagonist. Primary cultured rat prostate basal cells used as cell growth selective control. The growth-inhibitory effects were analyzed using MTT assay, and fluorochrome staining, flow cytometry, and immunoblotting were employed to illustrate the possible mechanisms. When treated with icaritin for 24 to 72 h, cell growth was strongly inhibited (at 48 h IC(50) was 10.74+/-1.59 micromol/l, P<0.001) companied with a mitochondrial transmembrane potential (_Psim) drop. Meanwhile, few changes in IC(50) could be observed when co-incubated with ICI 182,780. Icaritin-induced growth inhibition was associated with G(1) arrest (P<0.05), and G(2)-M arrest depending upon doses. Consistently with G(1) arrest, icaritin increased protein expressions of pRb, p27(Kip1) and p16(Ink4a), while showed decrease in phosphorylated pRb, Cyclin D1 and CDK4. Comparatively, icariin has much lower effects on PC-3 cells and showed only weak G(1) arrest, suggesting a possible structure-activity relationship. These findings suggested a novel anticancer efficacy of icaritin mediated selectively via induction of cell cycle arrest but not associated with estrogen receptors in PC-3 cells.
authors: Institute of Pharmacology & Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 353 Yan'an Road, Hangzhou 310031, China. hx06@yahoo.com.cn
authors: Xin
authors: X
authors: Huang
authors: Danyan
authors: D
authors: Zhu
authors: Yijia
authors: Y
authors: Lou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004958:Estradiol / Q000494:pharmacology; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D020128:Inhibitory Concentration 50; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D005419:Flavonoids; D004958:Estradiol; C499403:icaritin; C056599:icariin