Dichloroacetate (DCA), a drug that has been used for many years in patients with metabolic disorders, has recently been gaining attention for its cancer-fighting capabilities. Studies in the lab have already shown its potential against lung, breast and glioblastoma cancer cells. Now a new study in the journal Gynecoogic Oncology finds that DCA might also be a promising therapy for endometrial cancer.
Endometrial cancer, which affects the lining of the uterus, is often treated with chemotherapy. But chemo can cause severe side effects because it kills healthy cells along with cancerous ones.
To learn what effect DCA might have on endometrial cancer, researchers at Harvard Medical School in Boston grew several different endometrial cancer cell lines in a culture along with different doses of DCA. The higher the dose, the greater the effect DCA had on the cancer cells. Doses of between 5 mM and 10 mM appeared to be very effective against endometrial cancer.
DCA inhibits endometrial and other types of cancer cells in a unique way – by capitalizing on their unusual method of energy production. Unlike normal cells, which produce their energy in specialized units of the cell called mitochondria, cancer cells make energy through an inefficient cell-wide process called aerobic glycolysis. DCA forces the energy production into the mitochondria of the cancer cell, bringing the process back to normal. In doing so, DCA activates the cell’s process of programmed death, called apoptosis.
The researchers confirmed that DCA reduced the viability of endometrial cancer cells by triggering apoptosis, and by reducing the amount of a protein that would normally protect cancer cells from death. While it sped the destruction of cancer cells, DCA had no effect on healthy cells, which could mean fewer or no toxic side effects if DCA is ultimately used in human treatment.
The downside is that the most highly invasive endometrial cancer cells didn’t respond to DCA in the study, a finding that underscores the tenacity of the disease. “Cancer cells are the ultimate survivors. They often have altered traits in order to out-survive and out-proliferate normal cells,” explains Jason Wong, senior research laboratory manager at the Immaculata De Vivo Molecular Epidemiology Laboratory at Brigham and Women’s Hospital.
DCA does seem very promising for low to moderately invasive endometrial cancer cells, though. “Based on experiments performed thus far on the benchtop and in mouse models, we believe DCA is a very promising cancer therapeutic agent,” Wong says. “However, it is important to curb our enthusiasm until clinical trials in humans are complete. Most therapeutic agents that have shown promise in animal models have often failed to show adequate safety and efficacy in humans.”
Currently, a Phase I clinical trial is underway at the University of Alberta in Canada to investigate a safe dose for humans. Future research will also look at the potential benefit of DCA on other types of cancers, including ovarian cancer, and try to determine why some cancer cells seem to be more resistant to the drug than others, Wong says.
Wong JYY, Huggins GS, Debidda M, Munshi NC, De Vivo I. Dichloroacetate induces apoptosis in endometrial cancer cells. Gynecologic Oncology. 2008. doi:10.1016/j.ygyno.2008.01.038.