Cytogenetic effects of Jacareubin from Calophyllum brasiliense on human peripheral blood mononucleated cells in vitro and on mouse polychromatic erythrocytes in vivo.

Autor: García-Niño WR; Department of Toxicology, Centre for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Av. IPN 2508, San Pedro Zacatenco, GA Madero, Ciudad de México, CP 07360, Mexico., Estrada-Muñiz E; Department of Toxicology, Centre for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Av. IPN 2508, San Pedro Zacatenco, GA Madero, Ciudad de México, CP 07360, Mexico., Valverde M; Department of Genomic Medicine and Environmental Toxicology, Biomedical Research Institute, National University of Mexico (UNAM), Ciudad de México, CP 04510, Mexico., Reyes-Chilpa R; Department of Natural Products, Chemistry Institute, National University of Mexico (UNAM), Ciudad de México, CP 04510, Mexico., Vega L; Department of Toxicology, Centre for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Av. IPN 2508, San Pedro Zacatenco, GA Madero, Ciudad de México, CP 07360, Mexico. Electronic address: lvega@cinvestav.mx.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2017 Nov 15; Vol. 335, pp. 6-15. Date of Electronic Publication: 2017 Sep 22.
DOI: 10.1016/j.taap.2017.09.018
Abstrakt: Jacareubin is a xanthone isolated from the heartwood of Calophyllum brasiliense with antibacterial and gastroprotective properties and the intention for clinical use as an anti-cancer treatment (due to the similar chemical structure to other anti-neoplastic drugs) requires an investigation of whether this compound can generate adverse effects on non-transformed cells. Jacareubin (0.5-1000μM in DMSO) was more cytotoxic on phytohemagglutinin (PHA)-stimulated normal human peripheral blood mononuclear cells (PBMCs; IC 50 at 72h by MTT: 85.9μM) than on G 0 phase-PBMCs (IC 50 315.6μM) using trypan blue exclusion and formazan metabolism assays. Jacareubin had lower toxicity on PBMCs than Taxol (1μM). Jacareubin presented cytostatic activity because it inhibited PHA-stimulated PBMCs proliferation (from 2.5μM; CFSE dilution and replication index). Jacareubin induced PBMCs arrest in G 0 /G 1 phase of the cell cycle (from 5μM) as evaluated by DNA content. Moreover, Jacareubin generated genotoxicity by breaking DNA strands selectively in PHA-stimulated PBMCs (from 5μM) rather than on resting PBMCs using the single-cell gel electrophoresis assay and increasing the frequency of micronucleated (MN) PBMCs in vitro (from 5μM) and frequency of hypodiploid cells (from 10μM). When 100mg/kg Jacareubin was injected i.p. into mice (a fifth of the LD 50 ; 0.548g/kg. Approximately to 300μM in vitro), we observe no increase in the MN level in bone marrow cells. Jacareubin can be consider for further anti-tumoural activity due to its preferential genotoxic, cytotoxic and cytostatic actions on proliferating cells rather than on resting cells and the lack of in vivo genotoxicity.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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