Anthrapyrazoles are potent
cytotoxic agents that intercalate into
DNA, causing
DNA strand breaks, inhibition of
DNA synthesis and
topoisomerase II. In this study, we investigated the in vitro cytotoxic activity of two
anthrapyrazole analogues (AP-10 and AP-11) in human prostate (DU-145) and testicular (NTERA-2)
carcinoma cells. The cytotoxic activity of these analogues was determined using the MTS cell growth inhibition assay. The IC50 of
AP-10 on NTERA-2 and DU-145 cells was found to be 0.2 and 0.4 microM, respectively. AP-11 inhibited cell growth with an IC50 value of 1.2 microM (NTERA-2) and 3.2 microM (DU-145). Using
trypan blue dye exclusion assay, we were able to confirm the cytotoxic effect of
AP-10 and AP-11 on DU-145 cells, thereby distinguishing it from the
cytostatic effect. To determine whether cells were able to recover after exposure to the
anthrapyrazole analogues, DU-145 and NTERA-2 cells were exposed to the IC50 concentration of
AP-10 and AP-11. After a 1-h exposure, fresh media containing either
testosterone or
dihydrotestosterone were added daily for five days and the cell growth rate was compared to the control. Although cells exposed to
AP-10 and AP-11 were able to recover, they never attained the growth rate observed in the control cultures. The DNA fragmentation assay did not provide evidence of apoptosis. In conclusion, our results demonstrated that
AP-10 had a higher cytotoxic activity than AP-11, and apoptosis appeared not to be involved in the
biological activity of these compounds.