DIsulfiram Updates?  

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luce
 luce
(@luce)
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Joined: 2 years ago
Posts: 4
28/04/2019 6:27 am  

Have you had a chance to look further into DFF and copper? I’m pretty sure not all types of cancer cells accumulate zinc at levels higher than normal cells. I am pretty sure breast cancer cells do, melanoma perhaps too, but from what I read, most cancer cells do not. (But I’ve read many times that cancer cells have generally a higher need for and concentration of copper than normal ones. There was a study a year ago in Stanford where they used copper  isoform as a PET scan tracer in breast cancer, and it showed the tiniest mets, reportedly.) Since the increased (vs normal cells) demand for the metal that DSF binds to is what gets DSF into cancer cells, copper may be more effective for some or many cancers. But copper supplementation terrifies me. But so would iron, and that works with artemisinin. Also, do we really want DSF to chelate our zinc supply, given that a higher zinc:copper ratio seems favorable but is difficult to achieve? It would be interesting to know if DSF has a preference for chelating one metal over another. I keep meaning, then forgetting to, write to some study investigators for insights. The way I’m interpreting the research so far, it would be best to use whichever of those two metals your cancer cells are hoarding at higher levels than normal cells. If, say, your cancer cells use only about as much zinc as your healthy cells, the DSF would be dispersed throughout your body rather than preferentially be attracted by and thereby attack your cancer cells. I could be wrong, of course; I’m not a scientist. Would love to get educated input!!! I mean, sure, I get that DSF is a zinc ionophore, and that that’s a way of getting more zinc (and reach toxic levels) into cancer cells that otherwise wouldn’t accumulate it, but how would that not also affect healthy cells, if those cancer cells wouldn’t have a higher demand for zinc to start with?

Here’s a paper that suggests that disulfiram has an affinity for copper over zinc, and forms a more stable complex with copper than with any other metal. Therefore, while it is terrifying to supplement copper when one has cancer, it looks copper may be the preferable metal to use with DSF, especially if one’s cancer accumulates copper. (I’m trying to find out if mine does.) I still don’t understand why the protocols in the trials call for taking copper in the evening, DSF in the morning, since one wants a complex to form. It that to prime the cancer cells with copper, or to get copper into the circulation first? I believe DSF gets cleaved into its active metabolites in the acidity of the stomach, then forms the complex in the blood. Would that explain the timing of dosing? Anyway, here’s the paper. It’s not in cancer but tuberculosis. I’m posting it in an effort to elucidate how DSF interacts with metals, while trying to decide whether to use it or not, and while supplementing with which metal. I am starting to think that zinc supplementation would still be safe and maybe even a good idea while on DSF and copper. (I’m deducing this from the paper, perhaps incorrectly.)I would love your opinion. Thanks 

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ovidiu
(@ovidiu)
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Joined: 3 years ago
Posts: 4
28/04/2019 7:38 pm  

Plain DSF is of very limited use against cancer, in vivo, because most of the activity is lost by the metabolites. The current research tries to deliver DSF or DSF / Cu directly to tumors, through liposomes, nanoformulations, etc. Check this article "Investigation of the key chemical structures involved in the anticancer activity of disulfiram in A549 non-small cell lung cancer cell line." PMID: 30031402.

It says "S-methylated diethyldithiocarbamate (S-Me-DDC), one of the major metabolites of DS in liver, completely lost its in vitro anticancer activity".


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Daniel
(@daniel)
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Joined: 4 years ago
Posts: 306
08/05/2019 1:49 am  

Very interesting question Luce. I will think about it and come back with a reaction. For your cancer type you could check the zinc transporters here https://www.proteinatlas.org

Here is a post I wrote on Zinc in case you haven't seen that yet: https://www.cancertreatmentsresearch.com/unlocking-zincs-potential-to-fight-cancer/

Kind regards,
Daniel 


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