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Updated: Aug 17, 2026
Optimizing Tubulin Yield from Porcine Brain Tissue
Published on: October 11, 2024
Review: tubulin function, action of antitubulin drugs, and new drug development
Federico Pellegrini1, Daniel R Budman
1Experimental Therapeutics Section, Don Monti Division of Oncology, North Shore University Hospital, New York University School of Medicine, Manhasset, New York 11030, USA.
Abstract:
Anticancer agents that interfere with microtubulin function are in widespread use in man and have a broad spectrum of activity against both hematological malignancies and solid tumors. The mechanisms of actions of these agents have been better defined during the past decade, indicating that there are distinct binding sites for these agents and that they interfere with microtubulin dynamics (growth and shortening of tubules) at low concentrations and only evoke microtubulin aggregation or dissociation at high concentrations. Tubulin has been recently described in the nucleus of cells and in mitochondria. Downstream events from tubulin binding are believed to be critical events for the generation of apoptosis in the malignant cell. The effects of vinca alkaloids and taxanes are distinct, suggesting that the interference with the tubulin cap by high-affinity binding of effective agents is not the only mechanism of cytotoxic effect, and the low-affinity binding of drug, which distorts microtubulin function, may also be important. The epothilones share some of the binding characteristics of the taxanes and are in clinical trials because of cytoxic activity in taxane resistant cells. Tubulin has additional target sites for anticancer drugs including interference with the binding and function of microtubule associated proteins and interference with motor proteins which are essential for the transport of substances within the cell. Because many of these microtubule associated proteins have an ATP binding site, both computer-aided design and combinatorial chemistry techniques can be used to make agents to interfere with their function analogous to imatinib mesylate (Gleevec). Agents that interfere with the motor protein kinesin are entering clinical trials.
Insights
Anticancer drugs targeting microtubule function are vital for treating various cancers. New research reveals distinct drug binding sites and mechanisms, including interference with microtubule dynamics and associated proteins, leading to cancer cell death.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Microtubule-targeting anticancer agents are widely used against hematological malignancies and solid tumors.
- Understanding their mechanisms, including distinct binding sites and effects on microtubule dynamics, is crucial for developing new therapies.
- Recent discoveries highlight tubulin's presence in the nucleus and mitochondria, suggesting broader roles in cellular processes.
Purpose of the Study:
- To elucidate the diverse mechanisms of action for microtubule-targeting anticancer agents.
- To explore novel therapeutic strategies by targeting tubulin, microtubule-associated proteins, and motor proteins.
- To investigate the potential of epothilones in overcoming taxane resistance.
Main Methods:
- Review of existing literature on microtubule-targeting agents, including vinca alkaloids, taxanes, and epothilones.
- Analysis of tubulin binding sites and their impact on microtubule dynamics (polymerization and depolymerization).
- Exploration of computational and chemical techniques for designing drugs targeting microtubule-associated and motor proteins.
Main Results:
- Microtubule agents exhibit distinct binding sites and mechanisms, affecting microtubule dynamics at low concentrations and causing aggregation/dissociation at high concentrations.
- Both high-affinity and low-affinity drug binding contribute to cytotoxic effects.
- Epothilones show promise in treating taxane-resistant cancers.
- Novel targets include microtubule-associated proteins and motor proteins like kinesin, with agents in clinical trials.
Conclusions:
- Microtubule-targeting agents represent a significant class of anticancer drugs with diverse mechanisms.
- Further research into tubulin, associated proteins, and motor proteins offers new avenues for cancer therapy development.
- Targeting these components, potentially using computer-aided design, could overcome drug resistance and improve treatment outcomes.
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