Molecular and cellular interactions between intoplicine, DNA, and topoisomerase II studied by surface-enhanced Raman scattering spectroscopy

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 topoisomer...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1993-10, Vol.53 (20), p.4784-4790
Main Authors: Morjani, H, Riou, J F, Nabiev, I, Lavelle, F, Manfait, M
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - metabolism
Binding Sites
Cancer
Cattle
Cell Division - drug effects
Cell Survival - drug effects
DNA - chemistry
DNA - metabolism
DNA Topoisomerases, Type II - chemistry
DNA Topoisomerases, Type II - isolation & purification
DNA Topoisomerases, Type II - metabolism
DNA, Superhelical - metabolism
Engineering Sciences
Humans
Indoles - chemistry
Indoles - metabolism
Indoles - toxicity
Kinetics
Leukemia, Erythroblastic, Acute
Life Sciences
Nucleic Acid Conformation
Optics
Photonic
Plasmids
Protein Conformation
Pyridines - chemistry
Pyridines - metabolism
Pyridines - toxicity
Spectrum Analysis, Raman - methods
Thymus Gland - enzymology
Tumor Cells, Cultured
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Summary: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.
ISSN:0008-5472
1538-7445