title: Effect of justicidin B - a potent cytotoxic and pro-apoptotic arylnaphtalene lignan on human breast cancer-derived cell lines.
abstract: Justicidin B produced by genetically transformed cultures of Linum leonii was tested for cytotoxic activity and induction of apoptosis in MDA-MB-231 and MCF-7 breast cancer derived cell lines. The tested lignan evoked strong, concentration dependent cytotoxicity in both cell lines, whereby MCF-7 proved to be far more sensitive as compared to MDA-MB-231. The 24 h treatment of both cell lines increased the level of apoptotic DNA fragmentation; however the proapoptotic activity is completely inhibited if the cells are co-incubated with the non-selective pan-caspase inhibitor Boc-Asp(OMe)-fluoromethyl ketone (PCI), which implies that justicidin B, activates programmed cell death via caspase -dependent mechanisms. Exposure of MDA-MB-231 cells with justicidin B leads to concentration dependent decrease in the expression of NFkB; whereas the treatment of MCF-7, is consistent with strong increase in the expression of this transcription factor.
authors.affiliation: Lab of Experimental Chemotherapy, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University-Sofia, Bulgaria. gmomekov@cetrh.org
authors.forename: G
authors.initials: G
authors.lastname: Momekov
authors.forename: S
authors.initials: S
authors.lastname: Konstantinov
authors.forename: I
authors.initials: I
authors.lastname: Dineva
authors.forename: I
authors.initials: I
authors.lastname: Ionkova
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004148:Dioxolanes / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D017705:Lignans / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004148:Dioxolanes; D017705:Lignans; C049719:justicidins