title: Molecular interplay between cdk4 and p21 dictates G0/G1 cell cycle arrest in prostate cancer cells.
abstract: This study examined the effect of 3, 9-dihydroxy-2-prenylcoumestan (pso), a furanocoumarin, on PC-3 and C4-2B castration-resistant prostate cancer (CRPC) cell lines. Pso caused significant G0/G1 cell cycle arrest and inhibition of cell growth. Molecular analysis of cyclin (D1, D2, D3, and E), cyclin-dependent kinase (cdk) (cdks 2, 4, and 6), and cdk inhibitor (p21 and p27) expression suggested transcriptional regulation of the cdk inhibitors and more significant downregulation of cdk4 than of cyclins or other cdks. Overexpression of cdk4, or silencing of p21 or p27, overcame pso-induced G0/G1 arrest, suggesting that G0/G1 cell cycle arrest is a potential mechanism of growth inhibition in CRPC cells.
authors.affiliation: Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
authors.forename: Thippeswamy
authors.initials: T
authors.lastname: Gulappa
authors.forename: Ramadevi Subramani
authors.initials: RS
authors.lastname: Reddy
authors.forename: Suman
authors.initials: S
authors.lastname: Suman
authors.forename: Alice M
authors.initials: AM
authors.lastname: Nyakeriga
authors.forename: Chendil
authors.initials: C
authors.lastname: Damodaran
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D050687:E2F1 Transcription Factor / Q000378:metabolism; D011564:Furocoumarins / Q000494:pharmacology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D034622:RNA Interference; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D011564:Furocoumarins; D016160:Retinoblastoma Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
keywords: Castration-resistant prostate cancer; Cell cycle arrest; Cyclin-dependent kinase; Cyclins; Growth inhibition