Action of free radical in podophyllic acid piperindyl hydrazone nitroxide radical on its antitumor activity and toxicity.

Z P Jia, R Wang, J W Xie, L T Xu
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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.

鬼臼酸胡椒酰腙氮氧化物自由基对其抗肿瘤活性和毒性的作用。
目的:通过与其自由基还原产物鬼臼酸胡椒酰腙(GP-1- h)的比较,研究自旋标记鬼臼毒素衍生物鬼臼酸胡椒酰腙(GP-1- h)中自由基对其抗肿瘤活性和毒性的影响。方法:用GP-1和GP-1- h处理小鼠可移植肿瘤后,测定其对小鼠可移植肿瘤生长的抑制作用;测定SGC-7901和L1210细胞的MTT甲酸形成、[3H]脱氧胸腺嘧啶([3H]TdR)掺入、细胞周期进展和有丝分裂指数;对小鼠急性毒性和免疫功能进行了检测。结果:在1/6和1/12 LD50剂量下,对Lewis肺癌的抑制率分别为60.3%和42.1% (GP-1)、38.9%和10.3% (GP-1- h);发现GP-1对P388、HePS和S-180的抗肿瘤活性比GP-1- h更有效。在体外实验中,GP-1对SGC-7901和L1210细胞的增殖和DNA合成的抑制作用比GP-1- h更强。GP-1和GP-1- h在G2/M期阻滞L1210细胞,G1期细胞数量相应减少,细胞有丝分裂指数升高;但GP-1- h的作用弱于GP-1。以1/4和1/8 LD50剂量治疗5 d后,发现GP-1和GP-1- h对小鼠免疫功能无显著差异。结论:GP-1比GP-1- h具有更强的抗肿瘤活性。自旋标记的鬼臼毒素衍生物GP-1中的自由基在其抗肿瘤活性中发挥了重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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