Effects of daunomycin on the microtubular network: a cytochemical study on a human melanoma cell line.
The interaction of daunomycin (DAU), an anthracyclinic antibiotic employed as antitumoral agent, with microtubules, has been investigated by cytochemical and morphological methods on a human melanoma cell line (H14). Results obtained indicated that DAU was able to modulate the microtubule reassembly in cells treated with colcemid; such an effect proved to be dose-dependent. In particular, it has been observed that a low dose of DAU (0.05 microM) seemed to favor the microtubule reassembly whereas a higher dose (0.10 microM) impaired this process. In addition, when the anthracyclinic antibiotic was employed together with colcemid, both the cell detachment and the depolymerization of microtubules induced by the mitotic poison were hampered. These effects were dose-dependent and were better accomplished when DAU was used at an equimolar or at higher dose than that employed for the antimicrotubular agent. Moreover, the treatment of cells with DAU alone induced the stabilization of the microtubules, making them more resistant to the action of antimicrotubular agents. This effect could in part explain the antagonistic action exerted by DAU against colcemid. These observations seem to confirm that the microtubular network is an important target involved in the mechanism of action of the anthracyclinic antibiotics.
Molinari
A
A
Laboratorio di Ultrastructure, Istituto Superiore di Sanità, Roma, Italy.
Calcabrini
A
A
Crateri
P
P
Arancia
G
G
D002448:Cell Adhesion / Q000187:drug effects; D003630:Daunorubicin / Q000494:pharmacology*; D003703:Demecolcine / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008545:Melanoma; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured
D003703:Demecolcine; D003630:Daunorubicin