Presentation Title

Understanding the Interaction between Eribulin and Tubulin

Start Date

November 2016

End Date

November 2016

Location

HUB 302-#63

Type of Presentation

Poster

Abstract

Eribulin is an anti-cancer microtubule-targeting agent (MTA) used primarily to treat metastatic breast cancer. It can effectively stop or slow down cancer progression by blocking cell division in cells. However, similar to other anti-cancer MTAs, it has some undesirable side effects, particularly peripheral neuropathy, which can be very painful and dose-limiting. Understanding how eribulin interacts with the tubulin protein, which constitutes the microtubule structure, at a molecular level can provide insight into the drug’s therapeutic effects and side effects. Work using mammalian tissue culture cells has provided some insight into how the drug blocks cell cycle progression, but many molecular details remain unknown. We are using the sea urchin egg model system because of its experimental advantages, including synchronous cell division cycles and the ability to conduct large-scale biochemical studies. Unfertilized eggs are arrested in a haploid state and contain a large amount of unpolymerized tubulin. Upon fertilization, the egg is activated to enter the mitotic cell cycle, and tubulin is rapidly polymerized into microtubules to form the mitotic spindle. Through a series of dose-response experiments, we have determined that the effective concentration of eribulin for cell division arrest in sea urchin fertilized eggs is 0.5 µM. Furthermore, we sought to determine the arrest point in the cell cycle using fluorescence imaging of DNA and microtubule structures. Although studies are still ongoing, preliminary results indicate that entry into M phase of the first mitotic cycle is blocked. A long-term goal is to purify and analyze eribulin-tubulin co-crystals from the eggs. Successful formation and analysis of these co-crystals may provide valuable information about the eribulin-tubulin interaction, as well as insight into eribulin’s effects on cell division and neuropathy.

This document is currently not available here.

Share

COinS
 
Nov 12th, 4:00 PM Nov 12th, 5:00 PM

Understanding the Interaction between Eribulin and Tubulin

HUB 302-#63

Eribulin is an anti-cancer microtubule-targeting agent (MTA) used primarily to treat metastatic breast cancer. It can effectively stop or slow down cancer progression by blocking cell division in cells. However, similar to other anti-cancer MTAs, it has some undesirable side effects, particularly peripheral neuropathy, which can be very painful and dose-limiting. Understanding how eribulin interacts with the tubulin protein, which constitutes the microtubule structure, at a molecular level can provide insight into the drug’s therapeutic effects and side effects. Work using mammalian tissue culture cells has provided some insight into how the drug blocks cell cycle progression, but many molecular details remain unknown. We are using the sea urchin egg model system because of its experimental advantages, including synchronous cell division cycles and the ability to conduct large-scale biochemical studies. Unfertilized eggs are arrested in a haploid state and contain a large amount of unpolymerized tubulin. Upon fertilization, the egg is activated to enter the mitotic cell cycle, and tubulin is rapidly polymerized into microtubules to form the mitotic spindle. Through a series of dose-response experiments, we have determined that the effective concentration of eribulin for cell division arrest in sea urchin fertilized eggs is 0.5 µM. Furthermore, we sought to determine the arrest point in the cell cycle using fluorescence imaging of DNA and microtubule structures. Although studies are still ongoing, preliminary results indicate that entry into M phase of the first mitotic cycle is blocked. A long-term goal is to purify and analyze eribulin-tubulin co-crystals from the eggs. Successful formation and analysis of these co-crystals may provide valuable information about the eribulin-tubulin interaction, as well as insight into eribulin’s effects on cell division and neuropathy.