General Description
The vinca alkaloids are extracted from the leavesof Catharanthus roseus (periwinkle), and were originally investigatedfor their hypoglycemic properties but latter foundto possess antineoplastic actions.The alkaloids are composedof a catharanthine moiety containing the indole subunitand the vindoline moiety containing the dihydroindolesubunit joined by a carbon–carbon bond. Vincristine and vinblastine differ only in the group attached to the dihydroindolenitrogen, which is a methyl group in vinblastine and a formylgroup in vincristine.
Resistance to the vinca alkaloids occurs by several differentmechanisms that are also associated with resistance toseveral high–molecular-weight molecules with diversemechanisms of action also used in treating cancer.Thismultidrug resistance (MDR) is also seen with the taxanes,epipodophyllotoxins, and the anthracyclines although theresistance is usually greatest to the principal agent to whichthe patient was exposed. The MDR has been associated withseveral proteins including permeability glycoprotein (Pgp)and multidrug resistance protein (MRP1), which function toactively secrete the molecules from the cell. There are severalinhibitors of Pgp such as calcium channel blockers andcyclosporine, which have been investigated to decrease drugefflux; however, these first-generation inhibitors were notsuccessful in reducing drug efflux. There are several neweragents that have proven to be more potent inhibitors of Pgp,but none is currently approved. An additional mechanism ofresistance involves altered forms of tubulin to which thevincas fail to bind.
Anticancer Research
Vincristine and vinblastine are extracted from Madagascar periwinkle, Catharanthusroseus. These are primarily used in combination with other chemotherapy drugs intreating various cancers such as lung cancer, leukemia, testicular cancer, breastcancer, and lymphomas (Shoeb 2006). Vinca alkaloids and their semisyntheticderivatives cause depolymerization of tubulin by specific binding to it, leading tothe arrest of metaphase of mitosis (Balunas and Kinghorn 2005). Vinblastine targetsactivator protein-1 (AP-1) signal pathways (Singh et al. 2016b).
