Proteasomes, the proteolytic machinery of the ubiquitin/ATP-dependent pathway, have a relevant role in many processes crucial for cell physiology and cell cycle progression. Proteasome inhibitors are used to block cell cycle progression and to induce apoptosis in certain cell lines. Here we examine whether proteasomal function is affected by the anti-tumour drug vinblastine, whose cytostatic ac...

Oligoanions such as sodium triphosphate or GTP prevent and/or reverse vinblastine-induced polymerization of tubulin. We now show that the anions of glutamate-rich extreme C termini of tubulin are similarly involved in the regulation of the vinblastine effect. Cleavage of the C termini by limited proteolysis with subtilisin enhances vinblastine-induced tubulin polymerization and abolishes the an...

Microtubule inhibitors such as vinblastine cause mitotic arrest and subsequent apoptosis through the intrinsic mitochondrial pathway. However, although Bcl-2 family proteins have been implicated as distal mediators, their precise role is largely unknown. In this study, we investigated the role of Bak in vinblastine-induced apoptosis. Bak was mainly monomeric in untreated KB-3 cells, and multime...

We report a case of a 39-year-old man with Hodgkin lymphoma who developed depressive symptoms after starting adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy and later exhibited sexual disinhibition in addition to cognitive dysfunction (mainly executive dysfunction). Seven months after the start of adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy, he was finally di...

The treatment of any of a wide variety of cells with vincristine or vinblastine results in the dissolution of cytoplasmic microtubules and the formation of both 90-100 A filaments and ordered arrays of hexagonally packed, circular structures (1-4) . These ordered structures have been named "microtubular crystals" (2, 3), and this nomenclature will be followed here with the awareness that conclu...

Vinblastine is an important antitumor agent that induces G(2)-M arrest and subsequent apoptosis in a wide variety of cell lines, but the molecular mechanisms that link mitotic arrest and apoptosis are poorly understood. The AP-1 transcription factor has been implicated in many critical cellular processes, including apoptosis, and is a major target of the c-Jun NH(2)-terminal kinase signaling pa...

Multidrug resistance mediated by P-glycoprotein may be an important cause of chemotherapy failure. Renal cell carcinoma is a disease known to demonstrate a high degree of intrinsic chemotherapy drug resistance, and this has been shown to be related to intrinsic overexpression of P-glycoprotein. Cyclosporine A and tamoxifen have been shown to reverse multidrug resistance in renal cell carcinoma ...

Differential toxicity of vincristine and vinblastine against cells of a cloned subline of human promyelocytic leukemia (HL-60/CI) was dependent on exposure conditions. During continuous ex posures of 48 h, vincristine and vinblastine were equitoxic with drug concentrations that inhibited proliferation rates by 50% of 7.6 and 8.1 nw, respectively. When cells were subjected to 4-h exposures and t...

Two microtubule-associated proteins, tau and the high molecular weight microtubule-associated protein 2 (MAP 2), were purified from rat brain microtubules. Addition of either protein to pure tubulin caused microtubule assembly. In the presence of tau and 10 microM vinblastine, tubulin aggregated into spiral structures. If tau was absent, or replaced by MAP 2, little aggregation occurred in the ...