Fusarubin and anhydrofusarubin, compounds isolated from Cladosporium species, induce anti-proliferative and pro-apoptotic effects in human cancer-derived cell lines

Cladosporium species are endophytic fungi that grow on organic matter and are consideredfood contaminants. The anti-microbial and anti-tumor naphthoquinones fusarubin (FUS) andanhydrofusarubin (AFU) were isolated using column chromatography from a Cladosporium speciesresiding inside Rauwolfia leaves. The impact of FUS and AFU on cell growth was assessed in acutemyeloid leukemia (OCI-AML3) and other hematologic tumor cell lines (HL-60, U937, and Jurkat).Treatment with FUS or AFU reduced the number of OCI-AML3 cells as evaluated by a hemocytometer.Flow cytometry analyses showed that this e ect was accompanied by diverse impairments in cellcycle progression. Specifically, FUS (20 or 10 g/mL significantly decreased the percentage of cells inS phase and increased the percentage of cells in G2/M phase, whereas AFU increased the percentageof cells in G0/G1 phase (50 and 25 g/mL) and decreased the percentage of cells in S (50 g/mL)and G2/M (50 and 25 g/mL) phases. Both substances significantly increased apoptosis at higherconcentrations. The e ects of FUS were more potent than those of AFU, with FUS up-regulating p21expression in a p53-dependent manner, as detected by Western blot analyses, likely the consequenceof decreased ERK phosphorylation and increased p38 expression (both of which increase p21 stability).FUS also decreased Akt phosphorylation and resulted in increased Fas ligand production andcaspase-8/3-dependent apoptosis. These results suggest that FUS and AFU inhibit proliferation andincrease apoptosis in cell lines derived from hematological cancers.