title: Cytotoxic effect of the biotechnologically-derived justicidin B on human lymphoma cells.
abstract: Purpose of work: The study was aimed to assess the antineoplastic activity of justicidin B in vitro and to search for its general toxicological profile in vivo. The anti-neoplastic activity of the arylnaphthalene lignin, justicidin B, was assessed in a panel of human lymphoma cell lines and compared with etoposide as a reference compound. A screening of the cytotoxicity after 24, 48 and 72 h exposure was performed by the MTT-dye reduction assay. Dose- and time-dependent cytotoxic effect was observed and the IC50 values ranged from 0.17 µM (RPMI-8226, 72 h) to 183 µM (U-266, 24 h) and more than 200 µM (HD-MY-Z, 24 and 48 h). Activation of caspase 3 and 8 was involved in the induction of programmed cell death in DOHH-2 cell line. NF-κB modulation occurred in DOHH-2 and HH cells. The general toxicity in mice after i.p. injection was also tested. The highest applied dose (50 mg/kg = 137.25 µM) did not show any toxicity. Justicidin B possesses definite and potent selective antineoplastic activity, related to its ability to induce programmed cell death in NHL-derived human cell lines at concentrations that can be reached in mice without toxicity.
authors.affiliation: Laboratory for Experimental Chemotherapy, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav str., 1000, Sofia, Bulgaria, yohanailieva@hotmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Ilieva
authors.forename: I
authors.initials: I
authors.lastname: Zhelezova
authors.forename: T
authors.initials: T
authors.lastname: Atanasova
authors.forename: M M
authors.initials: MM
authors.lastname: Zaharieva
authors.forename: P
authors.initials: P
authors.lastname: Sasheva
authors.forename: I
authors.initials: I
authors.lastname: Ionkova
authors.forename: S
authors.initials: S
authors.lastname: Konstantinov
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004148:Dioxolanes / Q000494:pharmacology* / Q000633:toxicity; D005047:Etoposide / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D006801:Humans; D017705:Lignans / Q000494:pharmacology* / Q000633:toxicity; D008223:Lymphoma; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004148:Dioxolanes; D017705:Lignans; D016328:NF-kappa B; C049719:justicidins; D005047:Etoposide; D020169:Caspases