[Dan D]

Antabuse as treatment for multiple myeloma

by Dan D on Sun Jul 01, 2012 12:17 am

This article is a few months ago, but I only just saw it (and don't recall seeing mention of it on this forum). Notably the combination of this drug (DSF) plus copper does not appear to have any adverse effects on normal hematopoietic cells.

Yes, so far the studies are limited to cells, but here we have an approved drug that has a known safety profile in humans.

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Disulfiram, an old drug with new potential therapeutic uses for human hematological malignancies

International Journal of Cancer
Vol. 131 Issue 5

Abstract

Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor currently used for the treatment of alcoholism. Here, we show that multiple myeloma (multiple myeloma) cell lines and primary cells from newly diagnosed and relapsed/resistant patients affected by multiple myeloma, acute myeloid and lymphoblastic leukemia are significantly sensitive to DSF alone and in combination with copper. These effects are present at doses lower than those achievable in vivo after DSF standard administration. The cytotoxic effect achieved by this treatment is comparable to that obtained by conventional chemotherapy and is absent in normal hematopoietic cells. In addition, we found that DSF plus copper induces loss of mitochondrial membrane potential, triggers reactive oxygen species (ROS) production and activates executioner caspases. DSF-copper-induced apoptosis and caspases activation are strongly reversed by antioxidant N-acetylcysteine, thus indicating a critical role of ROS. These results might suggest the use of the old drug DSF, alone or in combination with copper, in the treatment of hematological malignancies

[Dr. Ken Shain]

Re: Antabuse as treatment for multiple myeloma

by Dr. Ken Shain on Sun Jul 01, 2012 10:53 am

Very interesting. I was not aware of this article. Hopefully, they will continue to demostrate continued meainingful success in vivo models and potnetially get it into phase 1 trials. We need all of the strategies we can get. It would be very interesting to see where this strategy goes.
Thanks
k

[suzierose]

Re: Antabuse as treatment for multiple myeloma

by suzierose on Tue Jul 03, 2012 9:19 am

Disulfiram is a proteasome inhibitor.

"Disulfiram significantly inhibited breast cancer tumor growth (by 74%), associated with in vivo proteasome inhibition (as measured by decreased levels of tumor tissue proteasome activity and accumulation of ubiquitinated proteins and natural proteasome substrates p27 and Bax) and apoptosis induction (as shown by caspase activation and apoptotic nuclei formation).
In conclusion, inhibitions of proteasome induces cell death, especially in the tumors, as metastatic ocular melanoma.
Disulfiram inhibited both NF-kappaB nuclear translocation and DNA binding activity. The inhibition of NF-kappaB contrasts its protective effect toward apoptosis hence facilitates it."

http://www.ncbi.nlm.nih.gov/pubmed/16206267
http://www.ncbi.nlm.nih.gov/pubmed/17079463