ABSTRACT. The search for new and effective antitumor agents with fewer cytotoxic side effects on normal tissue has increasingly become important. Lapachol, a natural organic compound isolated from the lapacho tree (Tabebuia avellandedae), is chemically identified as belonging to the naphthoquinone group and is known for its antiinflammatory, analgesic and antibiotic properties, although there are questions about its effectiveness for treating neoplasic cells. We evaluated the antitumoral effects of lapachol by testing for clones of epithelial tumors in Drosophila melanogaster. Seventy-two-hour old larvae bred from wts/TM3, Sb 1 females and mwh/mwh males, were treated with different concentrations of lapachol (20, 40 and 60 µg/mL). Lapachol alone did not significantly increase the number of epithelial tumors. However, lapachol did significantly reduce the number of tumors provoked by doxorubicin.
Antioxidant vitamins are able to deactivate highly bioactive molecules, such as free radicals, that are generated during cellular biochemical processes. Doxorubicin (DXR) is a cancer chemotherapeutic agent that generates free radicals as a byproduct. In the present study, the Drosophila melanogaster somatic wing spot test was used to evaluate the effects of a mixture of vitamins (Vitamins C, E, and beta-carotene) and minerals (copper, selenium, and zinc), commercially known as Vitergan Zinc Plus, on the genotoxicity of DXR in standard and high-bioactivation crosses of flies. 12.5, 25, and 50 mg/ml of the vitamin/mineral mixture by itself was nongenotoxic in the trans-heterozygous descendants of both crosses, while the mixture produced a significant reduction in the genotoxicity produced by 0.125 mg/ml DXR in the trans-heterozygous descendants of both crosses. The protective effect was observed when the larvae received either pre- or cotreatments of the multivitamin/mineral (MV) mixture. The results indicate that, under these experimental conditions, the MV mixture is not genotoxic; however, it protects against the genotoxic effects of the chemotherapeutic free-radical generator DXR.
This study investigated the genotoxicity of Lapachol (LAP) evaluated by wing spot test of Drosophila melanogaster in the descendants from standard (ST) and high bioactivation (HB) crosses. This assay detects the loss of heterozygosity of marker genes expressed phenotypically on the fly's wings. Drosophila has extensive genetic homology to mammals, which makes it a suitable model organism for genotoxic investigations. Three-day-old larvae from ST crosses (females flr3/TM3, Bds x males mwh/mwh), with basal levels of the cytochrome P450 and larvae of high metabolic bioactivity capacity (HB cross) (females ORR; flr3/TM3, Bds x males mwh/mwh), were used. The results showed that LAP is a promutagen, exhibiting genotoxic activity in larvae from the HB cross. In other words, an increase in the frequency of spots is exclusive of individuals with a high level of the cytochrome P450. The results also indicate that recombinogenicity is the main genotoxic event induced by LAP.
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