Vinblastine (also named Velban) is a natural alkaloid isolated from Vinca rosea, originally from Catharanthus (vinca) roseus. Vinblastine is used as chemotherapy medication such as an antimitotic agent. It is used as a treatment of breast cancer, testicular cancer, neuroblastoma, Hodgkin's and non-Hodgkins lymphoma, mycosis fungoides, histiocytosis and Kaposi's sarcoma. Its antitumor activity is thought to be due primarly to inhibition of mitosis at metaphase through interaction its interaction with tubulin (microtubules). Vinblastine binds specifically to microtubular proteins (tubulin) of the mitotic spindle, leading to crystallization of the microtubules (not dynamic anymore). In consequence, there is a mitotic arrest leading to the cell death. 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 permeability of the mitochondrial membrane, but is unable to do so due to the 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 capsases 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.

Vinblastine Pathway (New) References