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Celebration of Scholarship and Creative Activity 2021

“Combination of pro apoptotic drugs plus mild hyperthermia to induce programmed cell death in interphase cells”

Daniel Obi

Senior, Biology (Healthcare Science)

Abstract

Mild hyperthermia plus ABT-263 induces apoptotic-like characters in HeLa cells that are arrested in metaphase. However, they fail to induce apoptosis in interphase HeLa cells. We hypothesized that it could be due to three of the following reasons. First, we believe that it could be due to the fact that MCl-1 (myeloid cell leukemia- 1) naturally goes down during mitosis. During mitosis, MCl-1 levels drop resulting in intracellular activities that induce apoptosis. Secondly, an anti-apoptotic protein called B-cell lymphoma-2 (Bcl-2) decreases in amount when Abt-263 is added. Abt-263 inhibits Bcl-2 protein production, thereby promoting apoptosis. Thirdly, we believe that Bim ​―​a pro-apoptotic protein that is attached to microtubules released during mitosis has an effect in inducing apoptosis. So, it could be that Bim not being released in interphase cells prevents apoptosis. So, with all these three hypotheses, we believe that activating BIM and inhibiting Mcl-1 in interphase cells could induce apoptosis. The idea being that since BIM activation during mitosis induced apoptosis, forcefully activating it in interphase cells could induce apoptosis. Likewise, imitating the decrease of MCl-1 that is seen in mitotic cells in Metaphase cells could induce apoptosis.

Project Background

The work of Dr. What Paulson was doing in the chemistry department intrigued me. He was working on understanding why apoptosis induction in interphase cells were not successful but were in mitotic cells. His work would be very helpful in engineering effective and safe cancer treatments. Cancer remains one of the most devastating diseases in the world without a definitive cure. As of 2018, it was one of the leading causes of death in the world with 1,735,350 cases estimated to be diagnosed in the United States1​. Drugs and procedures like hyperthermia have been introduced to help treat cancer but much of those treatments are harsh and sometimes don’t work well enough. For instance, taxanes, epothilones and vinca alkaloids are all used in ovarian, breast, and lung cancer but they present major side effects to the nervous system. Other alternative treatments like surgery are even more risky and invasive due to a lot of complications. Instead of continuing with the current ways of getting rid of cancerous cells, merely understanding the key mechanism that drives apoptosis can allow scientists to derive drugs that can initiate the apoptosis mechanism to kill cancer cells.

 

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