title: Brassinin and its derivatives as potential anticancer agents.
abstract: The aim of the study was to investigate the anti-proliferative activity of brassinin and its derivatives on human cancer cell lines. We found that among twenty-one tested compounds, 1- methoxybrassinin exerted the most potent anti-proliferative activity in Caco-2 cells with IC₅₀ 8.2 (±1.2)μmoll(-1). The flow cytometric analysis revealed a 1-methoxybrassinin-induced increase in the sub-G1 DNA content fraction which is considered to be a marker of apoptotic cell death. Apoptosis was also confirmed by DNA fragmentation assay. Moreover, quantitative real-time PCR showed that 1-methoxybrassinin upregulated the expression of pro-apoptotic Bax and downregulated the expression of anti-apoptotic genes Bcl-2 and Bcl-xL. The compound also increased activity of caspase-3, -7, cleaved PARP and decreased intracellular GSH content. The present study has assessed the in vitro anti-proliferative potential of 1-methoxybrassinin. The results generate a rationale for in vivo efficacy studies with this compound in preclinical cancer models.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovak Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Chripkova
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovak Republic.
authors.forename: David
authors.initials: D
authors.lastname: Drutovic
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovak Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Pilatova
authors.affiliation: Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Safarik University, Kosice, Slovak Republic.
authors.forename: Jaromir
authors.initials: J
authors.lastname: Mikes
authors.affiliation: Department of Organic Chemistry, Institute of Chemical Sciences, Faculty of Science, Pavol Jozef Safarik University, Kosice, Slovak Republic.
authors.forename: Mariana
authors.initials: M
authors.lastname: Budovska
authors.affiliation: Department of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovak Republic.
authors.forename: Janka
authors.initials: J
authors.lastname: Vaskova
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Broggini
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovak Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Mirossay
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovak Republic. Electronic address: jan.mojzis@upjs.sk.
authors.forename: Jan
authors.initials: J
authors.lastname: Mojzis
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D013859:Thiocarbamates / Q000494:pharmacology*; D000094162:Phytoalexins
chemical_list: D000970:Antineoplastic Agents; D053148:Caspase 3; D053179:Caspase 7; D005978:Glutathione; D007211:Indoles; D011065:Poly(ADP-ribose) Polymerases; D019253:Proto-Oncogene Proteins c-bcl-2; D013859:Thiocarbamates; C089020:brassinin; D000094162:Phytoalexins
keywords: Anti-proliferative effect; Apoptosis; Brassinin; Indole phytoalexins