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14 thoughts on “D12B – Goddu”
Why was radiation also administered rather than just MGO and the positive control by itself? Is it to produce results more comparable to the treatments we currently give to cancer patients (i.e. radiation coupled with chemotherapy)?
Hey DeeDee! That’s exactly right—the goal in Discovery Lab this semester was to discover compounds that we can see work right away with radiation, rather than solely testing them in isolation and later revisiting their interactions with radiation. With that said, some groups did run experiments using just their compound without radiation and relevant negative/positive controls to investigate 1) how those compounds worked on their own and 2) what kind of relationship compounds had with radiation (synergistic, additive, antagonistic).
Why do you think your dose response data did not show a statistically significant difference?
This is a good question, Emma. We think that the dose response data didn’t generate a discernible curve, mostly due to having such a small data set. We were only able to run 2 replicates for that experiment, and in one of them the larvae yield was particularly small that week. I would think that in performing more trials (replicates) we might generate a cleaner, more discernible curve. Another consideration is that none of our doses may have been high enough to generate any response to begin-with. This is something we mention wanting to investigate in future directions.
For your future experiments, would you follow the same methods outlined here? Or would you like to use different experimentation methods?
Hey Katherine, for future experiments—like ones in which we would try a higher maximum concentration of MGO or administer it along with an efflux pump inhibitor, we would likely use the same base protocol to keep things as controlled and constant as possible. This would involve using the same fly husbandry techniques and controls, but with modifications in the negative control to include whatever efflux pump inhibitor was chosen.
Why is it that antibiotics are toxic to quickly replicating cells?
Hey Aimee! Good question. In my understanding, antibiotics can work through many different mechanisms to kill bacterial cells. Penicillin for example, inhibits an enzyme that forms the cross peptide-linkages in peptidoglycan which makes up its cell wall. I’m sure others can cause genome damage or work by different methods, but the key link between antibiotics and chemotherapies is that both inhibit the growth of cells that divide quickly.
What is the difference between the MGBA and the MGO which allows the MGBA to hinder enzymes in human leukemia? Is this difference a major one in regards to cancer treatment or is MGO still viable?
Hey Isaac, great question. MGBA works as a competitive inhibitor of S-adenosylmethionine (SAMe) decarboxylase in leukemia cells and it appears that could be due in part to the presence of certain functional groups that allows for this inhibition that MGO does not have. MGO may still prove to be a viable chemotherapy, but may ultimately be found to act through a different mechanism or as an inhibitor of a different key cancer cell enzyme.
Why did you choose MGO for your experiment specifically? If you could choose another substance other than MGO what would you choose?
Hey Bridget, originally we had actually wanted to investigate a compound called Convolamine which is a natural polyphenolic compound that has been used for centuries in Eastern, Ayurvedic medicine for many different things. We had trouble actually obtaining that compound however and so we looked at some alternative options, including current FDA-approved drugs with indications other than cancer treatment. This included Manuka honey, whose active ingredient is methylglyoxal. Given how effective it is as an antibiotic, we figured that there could be some overlap in cytotoxic properties and thought it was a very interesting prospect for that reason. If we could choose another substance, I think we would probably want to give Convolamine a shot!
If an efflux pump inhibitor were used in conjunction with your compound concentration of the compound inside the cell would likely be greater. Is there previous research to indicate that your drug will kill cells more effectively at a higher concentration?
Hey Delwin, the short answer is that there is no previous research indicating that MGO could be an effective chemotherapeutic with or without the added presence of an efflux pump inhibitor. We thought this would be an interesting avenue to test for the sole purpose of trying to better understand if drug efflux may potentially be a reason why this compound that is so toxic to bacteria (other quickly-dividing cells) is apparently not toxic in these eukaryotic model organism cells (and therefore potentially cancer cells).