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Pathway Description

Vinblastine Action Pathway

Homo sapiens

Drug Action Pathway

Created: 2013-08-22

Last Updated: 2025-01-29

Vinblastine (also named Velban) is a natural alkaloid isolated from the leaves of the Catharanthus roseus (commonly known as the Madagascar periwinkle). Vinblastine are used as chemotherapy medication such as an antimitotic anticancer agent. The mechanism of vinblastine is the inhibition of microtubule dynamics that would cause mitotic arrest and eventual cell death. As a microtubule destabilizing agent, Vinblastine stimulates mitotic spindle destruction and microtubule depolymerization at high concentrations. At lower clinically relevant concentrations, vinblastine can block mitotic progression. Unlike the taxanes, which bind poorly to soluble tubulin, vinblastine can bind both soluble and microtubule-associated tubulin. To be able stabilizing the kinetics of microtule, vinblastine rapidly and reversibly bind to soluble tubulin which can increase the affinity of tublin by the induction of conformational changes of tubulin. Vinblastine binds to β-tubulin subunits at the positive end of microtubules at a region called the _Vinca_-binding domain. Binding between vinblastine and solubale tubulin decreases the rate of microtubule dynamics (lengthening and shortening) and increases the duration of attenuated state of microtubules. Therefore, the proper assembly of the mitotic spindle could be prevented; and the tension at the kinetochores of the chromosomes could be reduced. Subsequently, chromosomes can not progress to the spindle equator at the spindle poles. Progression from metaphase to anaphase is blocked and cells enter a state of mitotic arrest. The cells may then undergo one of several fates. The tetraploid cell may undergo unequal cell division producing aneuploid daughter cells. Alternatively, it may exit the cell cycle without undergoing cell division, a process termed mitotic slippage or adaptation. These cells may continue progressing through the cell cycle as tetraploid cells (Adaptation I), may exit G1 phase and undergo apoptosis or senescence (Adaption II), or may escape to G1 and undergo apoptosis during interphase (Adaptation III). Another possibility is cell death during mitotic arrest. Alternatively, mitotic catastrophe may occur and cause cell death. Vinca alkaloids are also thought to increase apoptosis by increasing concentrations of p53 (cellular tumor antigen p53) and p21 (cyclin-dependent kinase inhibitor 1) and by inhibiting Bcl-2 activity. Increasing concentrations of p53 and p21 lead to changes in protein kinase activity. Phosphorylation of Bcl-2 subsequently inhibits the formation Bcl-2-BAX heterodimers. This results in decreased anti-apoptotic activity. One way in which cells have developed resistance against the vinca alkaloids is by drug efflux. Drug efflux is mediated by a number of multidrug resistant transporters as depicted in this pathway.

References

Vinblastine Pathway References

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Highlighted elements will appear in red.

Highlight Compounds

	Adenosine diphosphate
	Adenosine triphosphate
	Desacetylvinblastine
	Heme
	Phosphate
	Vinblastine
	Water

Highlight Proteins

	Canalicular multispecific organic anion transporter 1
	Canalicular multispecific organic anion transporter 2
	Cellular tumor antigen p53
	Cyclin-dependent kinase inhibitor 1
	Cytochrome P450 3A4
	Multidrug resistance protein 1
	Multidrug resistance-associated protein 1
	Multidrug resistance-associated protein 7
	RalA-binding protein 1
	Tubulin alpha-1B chain
	Tubulin beta-1 chain

Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.

Visualize Compound Data

		Adenosine diphosphate
		Adenosine triphosphate
		Desacetylvinblastine
		Heme
		Phosphate
		Vinblastine
		Water

Visualize Protein Data

		Canalicular multispecific organic anion transporter 1
		Canalicular multispecific organic anion transporter 2
		Cellular tumor antigen p53
		Cyclin-dependent kinase inhibitor 1
		Cytochrome P450 3A4
		Multidrug resistance protein 1
		Multidrug resistance-associated protein 1
		Multidrug resistance-associated protein 7
		RalA-binding protein 1
		Tubulin alpha-1B chain
		Tubulin beta-1 chain

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