Podophyllic acid piperidyl hydrazone nitroxide radical and etoposide on nucleic acids and protein metabolism of leukemia L7712 cells in vitro

Podophyllic acid piperidyl hydrazone nitroxide radical (GP-1) and etoposide (VP-16), derivatives of podophyllotoxin, inhibited DNA, RNA, protein and ATP synthesis of leukemia L7712 cells at a concentration of 5 micrograms/ml. Inhibitory extents were dependent on the exposure time from 3 to 24 h. The inhibitory rates of both drugs were about 15-66%. ID50 of GP-1 and VP-16 on the synthesis of L7712 cells at 24 h were 0.16 and 0.38 micrograms/ml, respectively. The dose-response curve of GP-1 was a parabolic one, while that of VP-16 was a straight line. The inhibition of GP-1 or VP-16 on DNA synthesis existed also after cells washing. It is suggested that the antitumor effects of GP-1 and VP-16 seem to be related to the damage of DNA template.