Cytotoxic constituents from Penicillium concentricum, an endophytic fungus from Trichocolea tomentella.

In our continuing effort to identify bioactive secondary metabolites from natural sources, the antiproliferative activity of 23 compounds, previously isolated from Penicillium concentricum, was assessed using the sulforhodamine B assay. The cytotoxic effect was determined against HeLa cervical, HT-29 colon, MDA-MB-321 breast, PC-3, and DU-145 prostate cancer cell lines. Compounds were also tested in the mitochondrial transmembrane potential (MTP) and nuclear factor kappa B (NF-κB) target-based assays. The results showed that 2-bromogentisyl alcohol (2) and 3-hydroxy-benzenemethanol (8) exhibited the highest cytotoxic activity against different cancer cell lines. Epoxydon (14) showed selectivity against DU-145 prostate cancer cells [inhibitory concentration 50 (IC50)=1.2 μmol/l]. Compounds 2, 8, 14, 18, 21 also induced damage of MTP (IC50=0.1, 0.2, 7.0, 9.6, and 1.8 μmol/l, respectively). In the NF-κB assay, only compound 8 exhibited potent inhibition (IC50=0.3 μmol/l). Compounds 2 and 14 showed cytotoxic activity and induction of damage in mitochondrial membrane potential while compound 8 inhibited NF-κB and MTP damage. Additionally, compound 14 with selectivity against DU-145 prostate cancer cells induced cell cycle arrested in G2/M phase. Thus, compounds 2, 8, and 14 could be useful leads in the development of new anticancer agents from natural sources.