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 psammapl in A (PSA), a naturally occurring biphenolic compound and its cytotoxicity to some human cancer cells including P-glycoprotein (Pgp)-overexpressing mu ltidrug resistant (MDR) cell line. PSA completely inhibited the DNA relaxat ion activity of Topo II at 75.0 mu M. It also completely inhibited the DNA decatenation activity of Topo II at 75.0 mu M, and showed about 50% inhibit ory activity at 18.8 mu M. In the cytotoxicity assay, the effective concent rations that cause 50% inhibition of cell growth (EC50) were 0.48 0.39, 1.8 3 and 3.76 mu M to A549, SK-OV-3 HCT15 and HCT15/CL02 (MDR cell line establ ished from HCT15 cells) cancer cells, respectively. In the presence of 8.0 mu M of verapamil (VER), a well-known MDR modulator; the EC50 of PSA to HCT 15/CL02 cells was reduced about 2.1 fold. Meanwhile, the EC(50)s of standar d 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 presenc e of 8.0 mu M VER, respectively. From the results, we conclude that PSA has Topo II inhibitory activity, and its cytotoxicity to cancer cells is not s o strongly affected by Pgp-associated MDR phenotype in comparison with some Topo II inhibitory anticancer drugs used in the clinic.