The redox couple avarol/avarone in the fight with malignant gliomas: the case study of U-251 MG cells

<p>This study aimed to screen <i>in vitro</i> antitumour activity of the redox couple avarol/avarone against the human malignant glioma cell line U-251 MG for the first time. Compared both with avarol and positive controls used (temozolomide and doxorubicin), avarone was found to be the most active compound with IC₅₀ value below 1 μM (IC₅₀ 0.68 ± 0.04 μM, 96 h). Considerable less DNA damage in the cells treated with avarol and avarone vs. doxorubicin (105 & 123% vs. 299%, respectively; untreated U-251 MG cells were used as a control, 100%), coupled with no sign of cytotoxicity against the normal human foetal lung fibroblast MRC-5 cells (IC₅₀ > 100 μM), has actually pointed out the importance of this marine sesquiterpenoid quinone structure as a promising lead compound in development of novel brain chemotherapeutics.</p

<i>In vitro</i> evaluation of cytotoxic and mutagenic activity of avarol

<p>The cytotoxicity of avarol, a main secondary metabolite of the Mediterranean sponge <i>Dysidea avara</i>, was <i>in vitro</i> screened by MTT assay against four human tumour cell lines. The colon HT-29 tumour cells practically showed to be the only sensitive ones towards this organic compound. No toxicity was found against the fetal lung fibroblast MRC-5 cells at the concentrations tested. In comparison with doxorubicin, used as a positive control, avarol actually exhibited at least 588-fold less toxicity towards normal MRC-5 cells. Finally, comet assay indicated that DNA fragmentation was almost fivefold higher upon the treatment with doxorubicin, compared to avarol. The obtained results have actually confirmed that avarol scaffold may contribute to development of new cytostatics inspired by nature.</p