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  • Title: Action of free radical in podophyllic acid piperindyl hydrazone nitroxide radical on its antitumor activity and toxicity.
    Author: Jia ZP, Wang R, Xie JW, Xu LT.
    Journal: Zhongguo Yao Li Xue Bao; 1999 Jun; 20(6):571-6. PubMed ID: 10678157.
    Abstract:
    AIM: 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. CONCLUSION: 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.
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