In vitro mechanism study of microtubule assembly inhibition by cis-dichlorodiammine-platinum(II). 1986

V Peyrot, and C Briand, and R Momburg, and J C Sari

The inhibitions of microtubule protein (MTP) and tubulin 6S polymerizations by cis-dichlorodiammine-platinum(II) (CDDP) have been investigated by turbidity measurements and electron microscopy. For 2.5 X 10(-4) M CDDP after 40 min contact time at 27 degrees, the inhibition was 60% for MTP (1.2 mg/ml) and nearly 90% for tubulin 6S (1.2 mg/ml). Microtubules were not present after a 1 hr contact time at 27 degrees with 2.5 X 10(-4) M CDDP. Free sulfhydryl group determinations with 5,5'-dithio-bis-(2-nitrobenzoate) (DTNB) showed that 20.10 (+/- 0.05) sulfhydryl groups were found per tubulin dimer. In the presence of excess CDDP, this number was reduced to 17.74 (+/- 0.05) after a 1 hr contact time at 27 degrees. By using CDDP-tubulin dialysis assays, the CDDP-tubulin complex formation was found to be an irreversible reaction through a covalent binding at the sulfhydryl group sites. By the DEAE filter paper method, CDDP was shown to slightly decrease vinca-alkaloid and colchicine bindings to tubulin likely by inducing a conformational change of the protein.

UI MeSH Term Description Entries
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
D008868 Microtubule Proteins Proteins found in the microtubules. Proteins, Microtubule
D008870 Microtubules Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS. Microtubule
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D003078 Colchicine A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (PERIODIC DISEASE). Colchicine, (+-)-Isomer,Colchicine, (R)-Isomer
D003545 Cysteine A thiol-containing non-essential amino acid that is oxidized to form CYSTINE. Cysteine Hydrochloride,Half-Cystine,L-Cysteine,Zinc Cysteinate,Half Cystine,L Cysteine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D014404 Tubulin A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE. alpha-Tubulin,beta-Tubulin,delta-Tubulin,epsilon-Tubulin,gamma-Tubulin,alpha Tubulin,beta Tubulin,delta Tubulin,epsilon Tubulin,gamma Tubulin

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