Noscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses
Noscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses
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DOI：
10.1007/s002620000109
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发表时间：
2000-07-01
影响因子：
5.8
通讯作者：
Kapp, JA
中科院分区：
文献类型：
--
作者：
Ke, Y;Ye, K;Kapp, JA
Noscapine, a phthalideisoquinoline alkaloid derived from opium, has been used as an oral anti-tussive agent and has shown very few toxic effects in animals or humans.最近，我们报道了诺斯卡品以化学计量与微管蛋白结合并促进微管聚合。 Noscapine 在体外引起肿瘤细胞有丝分裂生长停滞并诱导肿瘤细胞凋亡。先前的实验还表明，当胃肠外或通过洗胃给药时，诺斯卡品对小鼠具有有效的抗肿瘤活性。在这里，我们报告说，抗有丝分裂作用是那可品所特有的，因为密切相关的化合物不会抑制淋巴瘤细胞系的生长。此外，当将诺斯卡品加入饮用水中时，它可以有效减少淋巴瘤的生长并提高荷瘤小鼠的存活率。值得注意的是，诺斯卡品在肿瘤抑制剂量下对肾、肝、心脏、骨髓、脾或小肠几乎没有或没有毒性。此外，口服那斯卡品不会抑制主要免疫反应，该反应严重依赖于淋巴细胞的增殖。因此，我们的结果表明那可品有潜力成为治疗人类癌症的有效化疗剂。
Noscapine, a phthalideisoquinoline alkaloid derived from opium, has been used as an oral anti-tussive agent and has shown very few toxic effects in animals or humans. Recently, we reported that noscapine binds stoichiometrically to tubulin and promotes microtubule polymerization. Noscapine causes growth arrest of tumor cells in mitosis and induces apoptosis of tumor cells in vitro. Previous experiments also showed that noscapine has potent antitumor activity in mice when administered parenterally or by gastric lavage. Here, we report that the anti-mitotic effect was specific to noscapine since closely related compounds did not inhibit the growth of a lymphoma cell line. In addition, noscapine was shown to be effective in reducing the growth of the lymphoma and increasing the survival of tumor-bearing mice when administered in the drinking water. It is noteworthy that, noscapine showed little or no toxicity to kidney, liver, heart, bone marrow, spleen or small intestine at tumor-suppressive doses. Furthermore, oral noscapine did not inhibit primary immune responses, which are critically dependent upon proliferation of lymphoid cells. Thus, our results indicate that noscapine has the potential to be an effective chemotherapeutic agent for the treatment of human cancer.