Zhang X, Smith C D
Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Mol Pharmacol. 1996 Feb;49(2):288-94.
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.
维耳味吲哚酮是最近从蓝绿藻惠氏哈帕藻中分离出的一类新型生物碱。我们证明，用异硫氰酸维耳味吲哚酮C（现称为维耳味他汀）孵育人卵巢癌细胞SK - OV - 3和血管平滑肌细胞A - 10，会导致细胞增殖受到剂量依赖性抑制，这与有丝分裂期细胞百分比的增加相关。用维耳味他汀处理A - 10细胞会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细胞可防止因维耳味他汀而导致的微管解聚。维耳味他汀在体外抑制纯化微管蛋白的聚合，但不改变微管蛋白结合[3H]秋水仙碱或水解GTP的能力。此外，维耳味他汀不诱导拓扑异构酶/DNA复合物的形成。本研究结果表明，维耳味他汀是一种新的抗微管化合物，可规避多药耐药性，因此可能对耐药肿瘤的治疗有用。
