That is a great question! 50 C on the graph corresponds to 50 micrograms/mL of colchicine, which is a high dose of a chemotherapeutic that we have known about for a long time and is very effective at killing rapidly dividing cells. It targets the microtubules that are key during cell division to pull the chromosomes apart.
On your poster, it was discussed that your results had differed from previous experiments and that the use of a different model organism could have hindered these results. Is there a different organism, besides Drosophila Melanogaster, that you would recommend using to produce the desired results?
There were a couple studies done before using Bromelain as a chemotherapeutic that used human cancer cells in-vitro, specifically peritoneal mesothelioma and colorectal human cancer cells. There may be other cancer models that work well, the effectiveness of the model will depend on how similar the specific pathway targeted by the chemotherapeutic is between models.
Seeing that the administration of Bromelain did lower survival rates, is it possible a higher dosage would function better? Especially seeing as you mentioned Bromelain being a relatively inexpensive compound.
Also, what was the significance of conducting this experiment in a specific stage of the life cycle?
Absolutely! If we did further testing, investigating a max dosage 2x or 4x higher might well increase its effectiveness and potentially make it a statistical hit. One thing to note though is that natural proteases in the blood place a pretty low limit on plasma concentrations of Bromelain in humans, so higher concentrations would be difficult to achieve clinically. Also, we tested in third instar larvae because that is a period of very rapid cell growth, which does a good job of approximating cancer cells. It also allowed relatively simple quantification of how many flies survived/died due to the radiation + tested compounds.
Great presentation Joseph! I know you mentioned how it can be difficult to analyze the results because of the difference in fly and human physiology. What physiological similarities and/ or differences to you think drosophila and humans share/ don’t share.
That’s a good question! I think in the prior work we looked at, two main pathways for Bromelain to kill cancer cells were identified. One involved MUC-1, which is a protein that is overexpressed in some kinds of cancer cells and can protect them from chemotherapeutics. The other involved caspase dependent apoptosis triggered by the bromelain. So far we have not been able to find any information about either of these proteins in the fruit fly model, but if they are significantly different than there human homologs, that could contribute to differences in chemotherapeutic efficacy.
curesymposium.org 
Why was 50C so low on survival?
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That is a great question! 50 C on the graph corresponds to 50 micrograms/mL of colchicine, which is a high dose of a chemotherapeutic that we have known about for a long time and is very effective at killing rapidly dividing cells. It targets the microtubules that are key during cell division to pull the chromosomes apart.
LikeLike
On your poster, it was discussed that your results had differed from previous experiments and that the use of a different model organism could have hindered these results. Is there a different organism, besides Drosophila Melanogaster, that you would recommend using to produce the desired results?
LikeLike
There were a couple studies done before using Bromelain as a chemotherapeutic that used human cancer cells in-vitro, specifically peritoneal mesothelioma and colorectal human cancer cells. There may be other cancer models that work well, the effectiveness of the model will depend on how similar the specific pathway targeted by the chemotherapeutic is between models.
LikeLike
Seeing that the administration of Bromelain did lower survival rates, is it possible a higher dosage would function better? Especially seeing as you mentioned Bromelain being a relatively inexpensive compound.
Also, what was the significance of conducting this experiment in a specific stage of the life cycle?
LikeLike
Absolutely! If we did further testing, investigating a max dosage 2x or 4x higher might well increase its effectiveness and potentially make it a statistical hit. One thing to note though is that natural proteases in the blood place a pretty low limit on plasma concentrations of Bromelain in humans, so higher concentrations would be difficult to achieve clinically. Also, we tested in third instar larvae because that is a period of very rapid cell growth, which does a good job of approximating cancer cells. It also allowed relatively simple quantification of how many flies survived/died due to the radiation + tested compounds.
LikeLike
Great presentation Joseph! I know you mentioned how it can be difficult to analyze the results because of the difference in fly and human physiology. What physiological similarities and/ or differences to you think drosophila and humans share/ don’t share.
LikeLike
That’s a good question! I think in the prior work we looked at, two main pathways for Bromelain to kill cancer cells were identified. One involved MUC-1, which is a protein that is overexpressed in some kinds of cancer cells and can protect them from chemotherapeutics. The other involved caspase dependent apoptosis triggered by the bromelain. So far we have not been able to find any information about either of these proteins in the fruit fly model, but if they are significantly different than there human homologs, that could contribute to differences in chemotherapeutic efficacy.
LikeLike