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

- Jacareubin induces cell death in transformed human cells but not in normal cells.
- Jacareubin induces cell arrest in normal human cells.
- Jacareubin induces in vitro genotoxicity in transformed cells.
- Jacareubin has a good potential as an antineoplastic drug.

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 (0.5-1000 μM in DMSO) was more cytotoxic on phytohemagglutinin (PHA)-stimulated normal human peripheral blood mononuclear cells (PBMCs; IC50 at 72 h by MTT: 85.9 μM) than on G0 phase-PBMCs (IC50 315.6 μM) using trypan blue exclusion and formazan metabolism assays. Jacareubin had lower toxicity on PBMCs than Taxol (1 μM). Jacareubin presented cytostatic activity because it inhibited PHA-stimulated PBMCs proliferation (from 2.5 μM; CFSE dilution and replication index). Jacareubin induced PBMCs arrest in G0/G1 phase of the cell cycle (from 5 μM) as evaluated by DNA content. Moreover, Jacareubin generated genotoxicity by breaking DNA strands selectively in PHA-stimulated PBMCs (from 5 μM) rather than on resting PBMCs using the single-cell gel electrophoresis assay and increasing the frequency of micronucleated (MN) PBMCs in vitro (from 5 μM) and frequency of hypodiploid cells (from 10 μM). When 100 mg/kg Jacareubin was injected i.p. into mice (a fifth of the LD50; 0.548 g/kg. Approximately to 300 μM 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.