Action of free radical in podophyllic acid piperindyl hydrazone nitroxide radical on its antitumor activity and toxicity.
OBJECTIVE
To study the action of free radical in the spin-labeled podophyllotoxin derivative, podophyllic acid piperindyl hydrazone nitroxide radical (GP-1) on its antitumor activity and toxicity, by comparison with those of its free radical reduced product, podophyllic acid piperindyl hydrazone (GP-1-H).


METHODS
After treatment with GP-1 and GP-1-H, the inhibitory effects on the growth of mouse transplantable tumors were determined; MTT formazan formation, [3H]deoxythymidine ([3H]TdR) incorporation, cell cycle progression, and mitotic index of SGC-7901 or L1210 cells were measured; the acute toxicity and immune function of mice were assayed.


RESULTS
At doses of 1/6 and 1/12 LD50, the inhibitory rates against Lewis lung carcinoma were 60.3% and 42.1% (GP-1), 38.9% and 10.3% (GP-1-H), respectively; more effective antitumor activity of GP-1 against P388, HePS, and S-180 than that of GP-1-H were found. In vitro, GP-1 exhibited more powerful inhibitory effects on the proliferation and DNA synthesis of SGC-7901 and L1210 cells than GP-1-H. GP-1 and GP-1-H arrested the L1210 cells at G2/M phase with a corresponding decrease of the cells in G1 phase, and increased the mitotic index of the cells; but the effects of GP-1-H were weaker than those of GP-1. After treatment with doses of 1/4 and 1/8 LD50 for 5 d, no significant difference on immune function of mice between GP-1 and GP-1-H was found.


CONCLUSIONS
GP-1 had more powerful antitumor activities than GP-1-H. The free radical in the spin-labeled podophyllotoxin derivative, GP-1, played an important role in its antitumor activity.
Jia
Z P
ZP
Department of Biology, Lanzhou University, China.
Wang
R
R
Xie
J W
JW
Xu
L T
LT
D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D007939:Leukemia L1210 / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008940:Mitotic Index; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D013274:Stomach Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; C062702:podophyllic acid piperidyl hydrazone nitroxide radical; D011034:Podophyllotoxin