The effect of vinca alkaloid anticancer drug, vinorelbine, on chromatin and histone proteins in solution.
Vinorelbine (navelbin) belongs to vinca alkaloid anticancer drugs family with a broad spectrum of selective activity against mitotic microtubules. The present study is the first report demonstrating chromatin components as a novel target for vinorelbine in hepatocytes. The interaction was carried out in solution, employing fluorescence, UV spectroscopy and thermal denaturation techniques. Fluorescence emission spectra represented quenching of DNA chromospheres with drug and decreased fluorescence emission intensity in a dose-dependent manner. Binding of vinorelbine to chromatin induced very high hypochromicity and shifted DNA melting temperature to lower Tm. Vinorelbine binds to histone proteins with very high affinity when compared with the interaction of DNA intercalator anticancer drug, daunomycin, and the globular domain of the histones is considered as a main drug binding site. The results also showed that in the presence of vinorelbine, the absorbance of chromatin at 260 nm was decreased and the binding pattern was similar to daunomycin-chromatin complex. The results for the first time suggest that apart from tubulins, chromatin components can also be considered as a new target for this anticancer drug.
Rabbani-Chadegani
Azra
A
Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. rabbani@ibb.ut.ac.ir
Chamani
Elham
E
Hajihassan
Zahra
Z
D000042:Absorption; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002843:Chromatin / Q000187:drug effects* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003630:Daunorubicin / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012996:Solutions; D013050:Spectrometry, Fluorescence; D014466:Ultraviolet Rays; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D002843:Chromatin; D006657:Histones; D012996:Solutions; D014747:Vinblastine; D004247:DNA; D000077235:Vinorelbine; D003630:Daunorubicin