Inhibition of tubulin-microtubule polymerization by drugs of the Vinca alkaloid class.
نویسندگان
چکیده
A series of Vinca alkaloids were found to block polymerization of crude tubulin extracts of porcine brain in a dose-dependent manner. This appears to be a specific effect occurring at low concentrations of drug. The concentration of vinblastine that prevents polymerization by 50% was 4.3 x 10(-7) mole/liter for a tubulin concentration of 3.0 mg/ml, and this concentration is consistent with levels achieved in vivo following routine pharmacological doses in humans.
منابع مشابه
Vinca alkaloid-induced tubulin spiral formation correlates with cytotoxicity in the leukemic L1210 cell line.
The ability of a class of C-20' modified vinca alkaloid congeners to induce tubulin spiral formation was investigated relative to their ability to inhibit microtubule assembly, their cytotoxicity against a leukemic cell line, L1210, and their measured and calculated partition coefficients. These studies were prompted by the observation that the energetics of vinca alkaloid-induced tubulin spira...
متن کاملMultiple microtubule alterations are associated with Vinca alkaloid resistance in human leukemia cells.
Vinca alkaloids are used extensively in the treatment of childhood acute lymphoblastic leukemia (ALL) and despite their usefulness, drug resistance remains a serious clinical problem. Vinca alkaloids bind to the beta-tubulin subunit of the alpha/beta-tubulin heterodimer and inhibit polymerization of microtubules. Recent studies have implicated altered beta-tubulin isotype expression and mutatio...
متن کاملRegulation of Class II B-Tubulin Expression by Tumor Suppressor p53 Protein in Mouse Melanoma Cells in Response to Vinca Alkaloid
The continuous exposure of antimicrotubule drugs to tumors often results in the emergence of drug-resistant tumor cells with altered expression of several B-tubulin isotypes. We found that Vinca alkaloid enhanced expression of class II B-tubulin isotype (mTUBB2) in mouse B16F10 melanoma cells via alteration of the tumor suppressor p53 protein. Vincristine treatment stimulated an increase in mTU...
متن کاملMicrotubins: a novel class of small synthetic microtubule targeting drugs that inhibit cancer cell proliferation
Microtubule targeting drugs like taxanes, vinca alkaloids, and epothilones are widely-used and effective chemotherapeutic agents that target the dynamic instability of microtubules and inhibit spindle functioning. However, these drugs have limitations associated with their production, solubility, efficacy and unwanted toxicities, thus driving the need to identify novel antimitotic drugs that ca...
متن کاملMitotic Block of Human Blood Cells by Vinca herbacea, Catharanthus roseus and Colchicine Alkaloids
Catharanthus roseus (L.) G.Don is a plant which produces anticancer and anti-mitotic indole alkaloids. Colchicine is an anti-mitotic drug. Anti-mitotic effects of Vinca herbacea Waldst. & Kit. indole alkaloids is unknown. The study were evaluated the antimitotic effect of alkaloids of V. herbacea, Catharanthus roseus andcolchicineon mitosis and microtubule arrangement of human blood cells. In t...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cancer research
دوره 36 4 شماره
صفحات -
تاریخ انتشار 1976