Psammaplin A, a natural phenolic compound, has inhibitory effect on human topoisomerase II and is cytotoxic to cancer cells.

We evaluated the topoisomerase II (Topo II) inhibitory activity of psammaplin A (PSA), a naturally occurring biphenolic compound, and its cytotoxicity to some human cancer cells including P-glycoprotein (Pgp)-overexpressing multidrug resistant (MDR) cell line. PSA completely inhibited the DNA relaxation activity of Topo II at 75.0 microM. It also completely inhibited the DNA decatenation activity of Topo II at 75.0 microM, and showed about 50% inhibitory activity at 18.8 microM. In the cytotoxicity assay, the effective concentrations that cause 50% inhibition of cell growth (EC50) were 0.48, 0.39, 1.83 and 3.76 microM to A549, SK-OV-3, HCT15 and HCT15/CL02 (MDR cell line established from HCT15 cells) cancer cells, respectively. In the presence of 8.0 microM of verapamil (VER), a well-known MDR modulator, the EC50 of PSA to HCT15/CL02 cells was reduced about 2.1 fold. Meanwhile, the EC50s of standard Topo II inhibitory drugs such as doxorubicin, etoposide and mitoxantrone to HCT15/CL02 cells were reduced about 8.5, 9.3 and 8.1 fold in the presence of 8.0 microM VER, respectively. From the results, we conclude that PSA has Topo II inhibitory activity, and its cytotoxicity to cancer cells is not so strongly affected by Pgp-associated MDR phenotype in comparison with some Topo II inhibitory anticancer drugs used in the clinic.