Microtubule effects of welwistatin, a cyanobacterial indolinone that circumvents multiple drug resistance.
Microtubule effects of welwistatin, a cyanobacterial indolinone that circumvents multiple drug resistance.
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发表时间：
1996-02
影响因子：
3.6
通讯作者：
X. Zhang;C. Smith
中科院分区：
文献类型：
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作者：
X. Zhang;C. Smith
新近从蓝藻Hapalosiphon well witschii中分离得到一类新的生物碱。我们证明，SK-OV-3人卵巢癌细胞和A-10血管平滑肌细胞与异硫氰酸酯(现在称为威威司他汀)孵育后，细胞增殖受到剂量依赖性的抑制，这与细胞有丝分裂百分率的增加有关。用韦氏抑素处理A-10细胞可导致细胞微管可逆性耗竭，但不影响微丝。用紫杉醇预处理A-10细胞可阻止微管解聚对魏氏抑制素的反应。在体外，Welwistatin抑制纯化的微管蛋白的聚合，但不改变微管蛋白与[~3H]秋水仙碱的结合能力或对GTP的水解性。此外，韦氏他汀不能诱导拓扑异构酶/DNA复合体的形成。本研究结果表明，魏氏抑素是一种新型的抗微管化合物，可避免多重耐药，有望用于耐药肿瘤的治疗。
Welwitindolinones are a family of novel alkaloids recently isolated from the blue-green alga Hapalosiphon welwitschii. We demonstrate that incubation of SK-OV-3 human ovarian carcinoma cells and A-10 vascular smooth muscle cells with welwitindolinone C isothiocyanate, now termed welwistatin, results in dose-dependent inhibition of cell proliferation, which is correlated with increases in the percentage of cells in mitosis. Treatment of A-10 cells with welwistatin resulted in reversible depletion of cellular microtubules but did not affect microfilaments. Pretreatment of A-10 cells with paclitaxel prevented microtubule depolymerization in response to welwistatin. Welwistatin inhibited the polymerization of purified tubulin in vitro but did not alter the ability of tubulin to bind [3H]colchicine or to hydrolyze GTP. Also, welwistatin did not induce the formation of topoisomerase/DNA complexes. Results of the present study indicate that welwistatin is a new antimicrotubule compound that circumvents multiple drug resistance and so may be useful in the treatment of drug-resistant tumors.