In situ analysis of the action of Navelbine on various types of microtubules using immunofluorescence.
Preliminary clinical studies demonstrated that 5' nor-anhydro-vinblastine, Navelbine (NVB) has a broader antitumor activity and fewer neurotoxic effects than vinblastine or vincristine. The tectal plate anlage of mouse embryos at the earliest stages of neuronal differentiation were used to analyze and compare the effect of NVB, vincristine and vinblastine on axonal and mitotic microtubules after culture of post-implantation embryos in a medium containing the agent. All drugs are active on mitotic microtubules at the same concentration (0.1 mumol/L), inducing a depolymerization of microtubules and a blockade of cells at metaphase. At higher concentrations. NVB is the only one of the three drugs that induces a blockade of the cells at prophase. A depolymerization of axonal microtubules occurs at higher concentrations with NVB than with the two other vinca alkaloids. These results demonstrate that NVB is as active on mitotic microtubules and less active on axonal microtubules than vincristine and vinblastine. These findings can be related to the potent antitumor effect of the drug with minor neurotoxicity.
Binet
S
S
Laboratoire d'Anatomie, Faculté de Médecine, Paris, France.
Fellous
A
A
Lataste
H
H
Krikorian
A
A
Couzinier
J P
JP
Meininger
V
V
D000818:Animals; D000970:Antineoplastic Agents; D001369:Axons / Q000187:drug effects; D004622:Embryo, Mammalian; D005455:Fluorescent Antibody Technique; D008677:Metaphase / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D011418:Prophase / Q000187:drug effects; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014750:Vincristine / Q000008:administration & dosage / Q000494:pharmacology; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D014750:Vincristine; D014747:Vinblastine; D000077235:Vinorelbine