Abstract: “Protein tyrosine phosphatase-1β (PTP1β) is responsible for the negative regulation of insulin signaling and a therapeutic target for diabetes, cancer, and inflammation. Tremendous growth has been made in finding PTP1β inhibitors that comes from natural sources and exploring PTP1β regulatory mechanisms. The goal of our research is to see if thymoquinone, thymol, D-carvone, and carvacrol inhibit the enzyme protein tyrosine phosphatase-1β (PTP1β). Thymoquinone is a monoterpenoid and has been used as a drug for many things in recent history such as asthma, hypertension, diabetes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness and influenza. Thymol is a monoterpenoid phenol and is an isomer of carvacrol, it is currently not used as a drug, as an antiseptic and is present in some essential oils. Carvacrol is a monoterpenoid phenol which also has not been used as a drug before and, is currently used in perfumes and foods for its strong oregano smell and taste. Carvone is a terpenoid that has D and L enantiomers which have very different reactivity. In our research, we are using the D enantiomer which has been used for digestive drugs in humans and animals. The results from the inhibition of thymoquinone and D-carvone will be presented.”
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Great talk, Huguette and Max. The links between PTP1B and cancer are understandably complicated. Depending on the cancer/model, PTP1B ablation is correlated with either decreased tumor growth or with reduced survival. How do you think a treatment of this nature would be best implemented, considering that obesity is a risk factor in developing some forms of cancer?
Hello, thank you for your response. To answer your question, using safe inhibitors of PTP1B itself for treatment of obesity and type2 diabetes, like the ones we are studying are all part of essential oils and herbs used in seasoning/flavoring will not cause cancer. However, if the patient also develops cancer, the effect of PTP1b and its inhibition has different effects and should be treated on a case by case prognosis of the tumor. As effects of expression and inhibition of PTP1b in various kinds of cancer are not clearly understood yet and studies are ongoing.
This is the link to the research paper about the correlation of PTP1B and cancer https://doi.org/10.1016/j.bbapap.2009.09.018
Hello Max and Huguette. Nice study and good pace. Not sure but seemed like some of the video skipped, but was enough to get the gist of the talk. Two questions if I may. One, what did you dissolve the terpenoids in to obtain their solutions? I would think they would have low water solubility. Second, is it possible that there was some sort of side reaction going on with the phenolic terpenoids and pNPP instead of actual activation, and how would you test for this?
Hello! Thank you for the questions. I did skip some parts of the video unfortunately because of the minimum 5 minute limit on poster presentations. For your first question, we dissolved the terpenoids using DMSO because of the compounds’ solubility. For your second question, there was not any side reactions between pNPP and terpenoids. We tested this by having three wells of controls on a microplate where I added 10 uL of Assay buffer + 50 uL PTP1B + 40 uL pNPP and 10 uL of DMSO + 50 uL of PTP1B + 40 uL pNPP.
Thank you again and please let me know if you have any more questions or comments.
Hi Huguette and Max
Interesting study and nice team-work presenting the work together! I was surprised to see time-dependent inhibition of PTP1B. Usually that means covalent inhibition or slow tight-binding inhibition. Do you know if that is happening? It could be consistent with your observation that the ketone-containing molecules give you inhibition and the alcohols do not.
Anyway, nice job and good luck with the continuation of this work.
Wilfred van der Donk
Hello! Thank you so much for the comments. For your question, I actually have no idea how the mechanism works between the inhibitors and the enzyme. We have not done any studies about the mechanism but it is in our list of importance for future research. I am most likely sure that it is a covalent inhibition but we would still have to do experimental studies on it and hopefully I could give you a better answer when the time comes.