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Development of a new type of anticancer agent

Date:
January 20, 2016
Source:
University of Tsukuba
Summary:
Microtubules, one component of a cell’s skeleton, are hollow tubes formed from the polymerization of ?- and ?-tubulin, which are themselves important structural proteins of the mitotic spindle that equally separates chromosomes during cell division. As such, several ?/?-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, so the side effects of such treatments have become problematic. A wide variety of research has shown that ?-tubulin activates during cell division and that it is overexpressed in a portion of 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.
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FULL STORY

The g-tubulin-specific inhibitor gatastatin (right) developed by the research group from Glaziovianin A (AG1, left).
Credit: Image courtesy of University of Tsukuba

Microtubules, one component of a cell’s skeleton, are hollow tubes formed from the polymerization of α- and β-tubulin, which are themselves important structural proteins of the mitotic spindle that equally separates chromosomes during cell division. As such, 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, so the side effects of such treatments have become problematic.

A wide variety of research has shown that γ-tubulin activates during cell division and that it is overexpressed in a portion of 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.

University of Tsukuba Faculty of Life and Environmental Sciences Associate Professor Takeo Usui and Researcher Takumi Chinen, and University of Tsukuba Faculty of Pure and Applied Sciences Professor Hideo Kigoshi, 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, and have succeeded in developing the γ-tubulin specific inhibitor gatastatin.

Furthermore, using gatastatin their research has 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.


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Materials provided by University of Tsukuba. Note: Content may be edited for style and length.


Journal Reference:

  1. Takumi Chinen, Peng Liu, Shuya Shioda, Judith Pagel, Berati Cerikan, Tien-chen Lin, Oliver Gruss, Yoshiki Hayashi, Haruka Takeno, Tomohiro Shima, Yasushi Okada, Ichiro Hayakawa, Yoshio Hayashi, Hideo Kigoshi, Takeo Usui, Elmar Schiebel. The γ-tubulin-specific inhibitor gatastatin reveals temporal requirements of microtubule nucleation during the cell cycle. Nature Communications, 2015; 6: 8722 DOI: 10.1038/ncomms9722

Cite This Page:

University of Tsukuba. "Development of a new type of anticancer agent." ScienceDaily. ScienceDaily, 20 January 2016. <www.sciencedaily.com/releases/2016/01/160120092313.htm>.
University of Tsukuba. (2016, January 20). Development of a new type of anticancer agent. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2016/01/160120092313.htm
University of Tsukuba. "Development of a new type of anticancer agent." ScienceDaily. www.sciencedaily.com/releases/2016/01/160120092313.htm (accessed May 23, 2017).

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