Vindesine is a semi-synthetic vinca alkaloid derived from vinblastine. This drug is used for the treatment of acute leukemia, malignant lymphoma, Hodgkin's disease, acute erythraemia, and acute panmyelosis. It is differentiated from natural alkaloids by its eight-catharanine ring. Administered intravenously, Vindesine acts on tumorous cells in the body to suppress their growth. Its main mechanism of action works by binding microtubules that are formed during the M phase of mitosis. This ceases the polymerization of microtubules, effectively pausing the cell at its G2/M phase. The disarray of microtubules induces two proteins; cellular tumor antigen p53 and cyclin-dependent kinase inhibitor p21. The latter protein works to inhibit cyclin-dependent kinases in the cell, which disrupt the phosphorylation of the apoptosis inhibitor Bcl-2. Bcl-2 suppresses apoptosis by regulating the permeability of the mitochondrial membrane but is unable to do so due to interrupted phosphorylation. The former protein, p53, acts on BAK and BAX to enact conformational changes, creating pores in the mitochondrial membrane that allow the exit of cytochrome c. Cytochrome c further activates caspases in the cell, which cleave essential cellular proteins. In this way, p53 and p21 work alongside each other to promote apoptosis and terminate unhealthy cells. Vindesine is especially valuable as a drug because it binds specifically to mitotic microtubules, likely decreasing its neurotoxicity.

Vindesine Pathway (New) References