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This weekend, Bellarmine University will host The Kentucky Honors Roundtable. The roundtable gathers twice a year to give students an opportunity to present their research and creative work while faculty members exchange ideas about best practices. Ten Kentucky universities are participating. 

 

Trevor Stantliff, a senior biochemistry and molecular biology major from Louisville, is one of 16 Bellarmine students presenting their work at the event. We spoke to him about his research on lung cancer.

 

Trevor Stantliff: So actually, my initial research interest was with drug discovery. I spent two years forming several novel molecules that were tested by others in the lab for their ability to stop cancer cell growth. We saw the some of the best results of growth inhibition against lung cancer. Therefore, I moved forward with lung cancer as my "disease of choice."

 

Stantliff: The focus of my thesis is looking at how a small molecule is causing lung cancer cell death. We are looking at two options right now: is the drug causing the cell to self-destruct -- a process called Apoptosis -- or is the cell bursting open -- a process called Necrosis? When we discover what type of cell death is occurring, we can look further into what specific proteins are interacting with the drug.

 

BU: What were the results from this study? 

Stantliff: I am still in the midst of generating data so I can't say for sure what mechanism of action the cells are taking but here is what I have gathered so far:

1. The drug candidate is causing lung cancer cell death at low dosage.

2. When incubating the drug for a long duration, cells are destroyed to such an extent that there are only cellular remnants remaining.

3. Cells do not seem to be leaking lactate dehydrogenase when exposed to the drug. This is important because lactate dehydrogenase is what biochemists typically look for first when they look for necrosis.

 

I am currently delving deeper into the apoptosis pathway to see if the cell is killing itself when exposed to my drug. 

 

Stantliff: Once we see what type of cell death is occurring, additional structural modifications can be made to the drug to optimize cell death - further improving the therapeutic potential of the compound. 

 

Stantliff: I have been accepted and will be going to the University of Cincinnati College of Medicine to get my medical degree. I am also currently interested in continuing research in the field of infectious disease and vaccine development. 

 

Stantliff: This is not my first time presenting research in a public setting. I've had the opportunity to present research for two different research projects, one on breast cancer and cortisol, and the second on spinal muscular atrophy. This is, however, my first time presenting on this specific research project.

 

Yes, but in a good way. This presentation will be the pinnacle of my three years of undergraduate research on this project and it creates many emotions for me. Additionally, the Kentucky Honors Roundtable will prepare me for two conferences I have later this year. My abstract has been accepted to present at the Southern Regional Honors Conference in Memphis and at the American Society for Biochemistry and Molecular Biology's national conference in Orlando.

 

 

Investigations of the Mechanism of Action for Lung Cancer Cell Death by a 4-Trifluoromethoxy Substituted Chalcone Derivative, by Trevor Stantliff.

 

Chalcones are diphenyl compounds that serve as a natural precursor to flavanones in plants. Chalcones have been shown to have anticancer and antimicrobial activities. Chemoprevention activity of chalcones is of high interest in medicinal chemistry because of the simple laboratory synthesis via aldol condensation. Previously this lab created and screened a library of synthetic chalcones against A549 lung adenocarcinoma cell line for antiproliferation properties. We identified a strong drug candidate (4-tri-fluoromethoxy substituted chalcone) for A549 growth inhibition. However, the cause of inhibition by the substituted chalcone remains to be identified. I began to explore the mechanism of action of this drug by looking at physical characteristics of cell death with microscopy. Then, I conducted viability and cytotoxic assays such as MTS and Trypan blue for cell death quantification. Western Blots were run to identify dose dependency on the specific apoptotic proteins PARP and Caspase-3. Lactate Dehydrogenase Assay was used to quantify necrotic activity of the chalcone derivative. In this thesis, I present the results of the investigation into the apoptotic and necrotic cell death of lung cancer A549 cells by a chalcone derivative.