Recent progress in
cancer biology research has shown that abnormal proliferation in
tumor cells can be attributed to aberrations in cell cycle regulation, especially in G₁ phase. During the course of searching for microbial metabolites that affect cell cycle distribution, we have found that simaomicin α, a polycyclic
xanthone antibiotic, arrests the cell cycle at G₁ phase. Treatment of
T-cell leukemia Jurkat cells with 3 nM simaomicin α induced an increase in the number of cells in G₁ and a decrease in those in G₂–M phase. Cell cycle aberrations induced by simaomicin α were also detected in
colon adenocarcinoma HCT15 cells. Simaomicin α had antiproliferative activities in various tumor cell lines with 50% inhibitory concentration values in the range of 0.3–19 nM. Furthermore, simaomicin α induced an increase in cellular
caspase-3 activity and DNA fragmentation, indicating that simaomicin α promotes apoptosis. The
retinoblastoma protein phosphorylation status of simaomicin α-treated cell lysate was lower than that of control cells, suggesting that the target molecule of simaomicin α is in a pathway upstream of
retinoblastoma protein phosphorylation. In the course of evaluating polycyclic
xanthone antibiotics structurally related to simaomicin α, we also found that
cervinomycin A1 stimulated accumulation of treated cells in G₁ phase. These results indicate that the polycyclic
xanthones, including simaomicin α and
cervinomycin A1, may be candidate
cancer chemotherapeutic agents.