Vincristine Mechanism of Action
Vincristine binds avidly to tubulin, prevents microtubule formation, and inhibits mitosis, thereby leading to apoptosis in dividing cells. 1, 2
Primary Cellular Mechanism
Vincristine is a vinca alkaloid derived from the rose periwinkle plant (Catharanthus roseus) that specifically targets the microtubule system. 1, 3
The drug attaches to tubulin fibrils and prevents filament polymerization, which permanently inhibits mitosis in cancer cells by arresting dividing cells at the metaphase stage. 2, 3
This microtubule disruption leads to apoptosis (programmed cell death) in actively dividing cells. 1
Mechanism in Immune Disorders
Beyond its antimitotic effects, vincristine has additional mechanisms relevant to immune-mediated conditions:
In immune thrombocytopenia (ITP), the primary mechanism is inhibition of macrophage function, which reduces platelet phagocytosis. 1
The drug's effect in immune disorders may also be mediated by lymphocyte inhibition. 1
Antiangiogenic Properties
- Vincristine possesses multiple antiangiogenic qualities, including induction of endothelial cell apoptosis and potent inhibition of endothelial cell growth, migration, and in vitro capillary-like tube formation. 1
Pharmacokinetic Considerations
The FDA label confirms that vincristine's mechanism relates to inhibition of microtubule formation in the mitotic spindle, resulting in metaphase arrest. 2
Vincristine affects all dividing cells but has found particular utility in lymphoid malignancies, likely due to the high proliferation rate of these cells. 1
The drug does not penetrate well into cerebrospinal fluid, which explains why central nervous system leukemia can occur in patients otherwise responding to vincristine therapy. 2
Clinical Implications of Mechanism
Because vincristine affects all dividing cells indiscriminately, it causes significant toxicity, with peripheral neuropathy occurring in approximately 27.8% of patients due to disruption of neuronal microtubules. 1, 4, 5
The lack of significant bone marrow suppression at recommended doses (compared to other chemotherapeutic agents) makes vincristine particularly suitable for combination therapy regimens. 2
Autonomic nervous system effects (constipation, paralytic ileus, postural hypotension) result from vincristine's impact on autonomic nerve microtubules. 4, 5