DCA: Dichloracetate. Anti-Cancer Wonder Drug?

There’s been a bit of a buzz online about DCA or Dichloracetate as a “cheap and simple cure for cancer”. Well, maybe not THAT simple, but here are a few preliminary published studies that say there is definitely something to this direction of research. In fact, DCA is one of many substances that are being tested as part of “metabolic targeting”. What this means is that these drugs or substances are used to block essential parts of the metabolism of a cancer cell, while minimally disrupting the biological workings of normal cells. Not a new concept in general, but each strategy is contributing something in the overall fight against cancer. Again, these results are examples of preliminary work. More studies are anticipated before declaring this a major step in that direction. (NB. As you keep reading, the word “Apoptosis” means programmed cell death. This is something cancer cells do not do well. In other words, while normal cells in our body die off and get replaced predictably, cancer cells keep going and going and going etc. and not dying. )

First, from the Department of Medicine, University of Alberta, Edmonton, Canada.
“The unique metabolism of most solid tumours (aerobic glycolysis, i.e., Warburg effect) is not only the basis of diagnosing cancer with metabolic imaging but might also be associated with the resistance to apoptosis that characterises cancer. The glycolytic phenotype in cancer appears to be the common denominator of diverse molecular abnormalities in cancer and may be associated with a (potentially reversible) suppression of mitochondrial function. The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis. This reverses the suppressed mitochondrial apoptosis in cancer and results in suppression of tumour growth in vitro and in vivo. Here, we review the scientific and clinical rationale supporting the rapid translation of this promising metabolic modulator in early-phase cancer clinical trials.”
Br J Cancer. 2008 Oct 7;99(7):989-94. Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Michelakis ED, Webster L, Mackey JR. For more info: evangelos.michelakis@capitalhealth.ca

Our second example is from Harvard University. “A recent landmark study demonstrated that Dichloroacetate (DCA) treatment promoted apoptosis in lung, breast, and glioblastoma cancer cell lines by shifting metabolism from aerobic glycolysis to glucose oxidation coupled with NFAT-Kv1.5 axis remodeling. The objective of this study was to determine whether DCA induces apoptosis in endometrial cancer cells and to assess apoptotic mechanism. METHODS: A panel of endometrial cancer cell lines with varying degrees of differentiation was treated with DCA and analyzed for apoptosis via flow cytometry. Biological correlates such as gene expression, intracellular Ca(2+), and mitochondrial membrane potential were examined to assess apoptotic mechanism. RESULTS: Initiation of apoptosis was observed in five low to moderately invasive cancer cell lines including Ishikawa, RL95-2, KLE, AN3CA, and SKUT1B while treatment had no effect on non-cancerous 293T cells. Two highly invasive endometrial adenocarcinoma cell lines, HEC1A and HEC1B, were found to be resistant to DCA-induced apoptosis. Apoptotic responding cell lines had a significant increase in early and late apoptotis, a decrease in mitochondrial membrane potential, and decreased Survivin transcript abundance, which are consistent with a mitochondrial-regulated mechanism. DCA treatment decreased intracellular calcium levels in most apoptotic responding cell lines which suggests a contribution from the NFAT-Kv1.5-mediated pathway. DCA treatment increased p53 upregulated modulator of apoptosis (PUMA) transcripts in cell lines with an apoptotic response, suggesting involvement of a p53-PUMA-mediated mechanism. CONCLUSIONS: Dichloroacetate effectively sensitizes most endometrial cancer cell lines to apoptosis via mitochondrial, NFAT-Kv1.5, and PUMA-mediated mechanisms. Further investigation of the cancer therapeutic potential of DCA is warranted.”
Gynecol Oncol. 2008 Jun;109(3):394-402. Dichloroacetate induces apoptosis in endometrial cancer cells.
Wong JY, Huggins GS, Debidda M, Munshi NC, De Vivo I.