Molecular and cellular interactions between intoplicine, DNA, and topoisomerase II studied by surface-enhanced Raman scattering spectroscopy.
Fiche publication
Date publication
octobre 1993
Journal
Cancer research
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MORJANI Hamid, Pr NABIEV Igor
Tous les auteurs :
Morjani H, Riou JF, Nabiev I, Lavelle F, Manfait M
Lien Pubmed
Résumé
The surface-enhanced Raman scattering spectra of the new antitumoral agent, intoplicine (RP 60475, NSC 645008), and those of its complexes with DNA and topoisomerase II in vitro and in K562 cancer cells were obtained. Intoplicine was found to unwind DNA and to inhibit purified calf thymus topoisomerase II via a stabilization of the ternary cleavable complex. The intensity of the surface-enhanced Raman scattering spectrum of intoplicine was not modified by the addition of plasmid pBR322 or calf thymus DNA. In the complex of this antitumor agent with topoisomerase II, the signal of intoplicine was completely abolished, indicating that at least some portion of intoplicine binds to an internal part of the enzyme. During the formation of the ternary complex, intoplicine was released from the interior of the protein and formed hydrogen bonds via its hydroxyl and/or amino groups. Similar modifications of the intoplicine spectra were found by microsurface-enhanced Raman scattering spectroscopy of the compound in the nucleus of treated K562 cells. In contrast, intoplicine was found to be in a free form in the cytoplasm.
Mots clés
Animals, Antineoplastic Agents, metabolism, Binding Sites, Cattle, Cell Division, drug effects, Cell Survival, drug effects, DNA, chemistry, DNA Topoisomerases, Type II, chemistry, DNA, Superhelical, metabolism, Humans, Indoles, chemistry, Kinetics, Leukemia, Erythroblastic, Acute, Nucleic Acid Conformation, Plasmids, Protein Conformation, Pyridines, chemistry, Spectrum Analysis, Raman, methods, Thymus Gland, enzymology, Tumor Cells, Cultured
Référence
Cancer Res.. 1993 Oct;53(20):4784-90