Interaction of anthracyclinic antibiotics with cytoskeletal components of cultured carcinoma cells (CG5).
The effects of doxorubicin (adriamycin, ADR) and daunorubicin (daunomycin, DAU), two anthracyclinic antibiotics, on a human breast carcinoma cell line (CG5) were studied by cytochemical and morphological methods. Both ADR and DAU were capable of inducing the multinucleation and spreading phenomena, associated with a decrease of the cell growth rate. DAU appeared to be more effective than ADR at the tested concentrations (10(-5), 5 x 10(-5) mM), in affecting the cell growth as well as in inducing multinucleation. As revealed by scanning electron microscopy, spreading and multinucleation were accompanied by a remarkable redistribution of surface structures. Moreover, a dose- and time-dependent rearrangement of the underlying cytoskeletal components was clearly detected. In addition, both ADR and DAU at 5 x 10(-5) mM seemed to favor the rebuilding of microtubules after treatment with colcemid, while a higher dose (10(-4) mM) exerted the opposite effect. Furthermore, both anthracyclines prevented the action of the antimicrotubular agent. When recovered after treatment with cytochalasin B, in presence of ADR (or DAU) (5 x 10(-5), 10(-4) mM), cells showed a microfilament pattern rearranged differently as compared to that of cells recovered in anthracycline-free medium. The results reported here strongly suggest the involvement of actin and tubulin in CG5 cell response to ADR and DAU treatments. Thus, the cytoskeletal apparatus is confirmed as another target involved in the mechanism of action of anthracyclines.
Molinari
A
A
Department of Ultrastructures, Istituto Superiore di Sanità, Rome, Italy.
Calcabrini
A
A
Crateri
P
P
Arancia
G
G
D000199:Actins / Q000032:analysis / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000378:metabolism* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D003630:Daunorubicin / Q000494:pharmacology / Q000627:therapeutic use; D003703:Demecolcine / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D014404:Tubulin / Q000032:analysis / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
D000199:Actins; D000903:Antibiotics, Antineoplastic; D014404:Tubulin; D003571:Cytochalasin B; D004317:Doxorubicin; D003703:Demecolcine; D003630:Daunorubicin