Tubulin-Targeting Anticancer Drugs Made More Specific

Researchers have developed anticancer agents to target the proteins that help cancer cells to divide and multiply.

AsianScientist (Feb. 4, 2016) – Researchers have developed an anticancer agent that prevents cell division by selectively targeting γ-tubulin. Their research has been published in Nature Communications.

Microtubules, subcellular structures that give cells their shape, are hollow tubes formed when two structural proteins, α- and β-tubulin, join together in a process called polymerization.

Several α/β-tubulin inhibitory agents are used as therapeutic drugs against cancer cells which are undergoing vigorous cell division. However, microtubules perform important work even outside of cell division, and normal cells not undergoing division can be harmed as well—leading to undesirable side effects.

Previous research has shown that γ-tubulin activates during cell division and that it is overexpressed in some cancer cells, so it holds potential as a target protein for new anticancer agents, with few side effects. Despite this research, no specific inhibitors have thus far been discovered.

An international team of researchers from the University of Tsukuba in joint research with Heidelberg University, Okayama University, Tokyo University of Pharmacy and Life Sciences and RIKEN have synthesized and developed the α/β-tubulin inhibitors glaziovianin A and plinabulin, advancing the development of compounds that exhibit γ-tubulin inhibitory activity. Furthermore, they have succeeded in developing the γ-tubulin specific inhibitor gatastatin.

Their research has also shed light on the fact that γ-tubulin function is important in microtubule function in the late stages of cell division. The results of these studies provide knowledge linking to analyses of intracellular γ-tubulin function, as well as the development of new anticancer agents.

The article can be found at: Chinen et al. (2015) The γ-tubulin-Specific Inhibitor Gatastatin Reveals Temporal Requirements of Microtubule Nucleation During the Cell Cycle.

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Source: University of Tsukuba; Photo: Shutterstock.
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