title: Mechanisms of natural brassinosteroid-induced apoptosis of prostate cancer cells.
abstract: Brassinosteroids (BRs) are a group of polyhydroxylated sterol derivatives with important regulatory roles in various plant physiological processes. The aim of this study was to examine the mechanism of the antiproliferative activity of natural BRs 28-homocastasterone (28-homoCS) and 24-epibrassinolide (24-epiBL) in hormone-sensitive and -insensitive (LNCaP and DU-145, respectively) human prostate cancer cell lines. The effects of BRs on prostate cancer cells were surveyed using flow cytometry, Western blotting, TUNEL, DNA ladder assays and immunofluorescence analyses. The studied BRs inhibited cell growth and induced G(1) blocks in LNCaP cells accompanied by reductions in cyclin D(1), CDK4/6 and pRb expression. Following BR treatment of DU-145 cells, increases in proportions of cells in the G(2)/M phase of cell cycle were observed, accompanied by down-regulation of cyclins A and B(1). Changes in AR localization patterns in LNCaP cells treated with BRs were shown by immunofluorescence analysis. Furthermore, apoptotic detection methods demonstrated induction of apoptosis mediated by BRs in both cell lines, although changes in the expression of apoptosis-related proteins were modulated differently by 28-homoCS and 24-piBL in each cell line. The studied BRs seem to exert potent growth inhibitory and pro-apoptotic effects and could be therefore highly valuable new candidates for prostate anticancer drugs.
authors.affiliation: Laboratory of Molecular Pathology, Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech Republic. jana.steigerova@seznam.cz
authors.forename: Jana
authors.initials: J
authors.lastname: Steigerová
authors.forename: Lucie
authors.initials: L
authors.lastname: Rárová
authors.forename: Jana
authors.initials: J
authors.lastname: Oklešt'ková
authors.forename: Kateřina
authors.initials: K
authors.lastname: Křížová
authors.forename: Monika
authors.initials: M
authors.lastname: Levková
authors.forename: Michaela
authors.initials: M
authors.lastname: Sváchová
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Kolář
authors.forename: Miroslav
authors.initials: M
authors.lastname: Strnad
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D060406:Brassinosteroids / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002778:Cholestanones / Q000494:pharmacology; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D013260:Steroids, Heterocyclic / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D060406:Brassinosteroids; C530104:CCND1 protein, human; D002778:Cholestanones; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013260:Steroids, Heterocyclic; D019938:Cyclin D1; C070164:homocastasterone; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; C023623:brassinolide