Antidepressants And Blood Thinners Cause Brain Cancer Cells To Eat Themselves

Antidepressants And Blood Thinners Cause Brain Cancer Cells To Eat Themselves
Analysis of cell viability of equal numbers of human
 glioblastoma cells plated in a six-well cell culture dish,
determined by crystal violet staining for live cells. The cells
were treated for three days with a TCA (imipramine), the
anti-coagulant (ticlopidine) or the combination of two, at two
different concentrations. The purple color reflects millions of
live cancer cells in a well, whereas the clearing and lack of
purple stain is indicative of impaired proliferation and
survival (cell death) of the glioblastoma cancer cells.
(Credit: Douglas Hanahan.)
Scientists have been exploring the connection between tricyclic antidepressants and brain cancer since the early 2000s. There's some evidence that the drugs can lower one's risk for developing aggressive glioblastomas, but when given to patients after diagnosis in a small clinical trial, the antidepressants showed no effect as a treatment.
In a study appearing in Cancer Cell, researchers find that antidepressants work against brain cancer by excessively increasing tumor autophagy (a process that causes the cancer cells to eat themselves). The scientists next combined the antidepressants with blood thinners - also known to increase autophagy - as a treatment for mice with the first stages of human glioblastoma. Mouse lifespan doubled with the drug combination therapy, while either drug alone had no effect.
Mice received the combination therapy 5 days a week with 10-15 minute intervals between drugs. The antidepressant was given orally, and the other drug (the blood thinner or anti-coagulant) was injected. The data suggest that the drugs act synergistically by disrupting, in two different places, the biological pathway that controls the rate of autophagy - a cellular recycling system that at low levels enhances cell survival in stressful conditions. The two drugs work together to hyper-stimulate autophagy, causing the cancer cells to die.
"Importantly, the combination therapy did not cure the mice; rather, it delayed disease progression and modestly extended their lifespan," the researchers said. "It seems likely that these drugs will need to be combined with other classes of anticancer drugs to have benefit in treating gliblastoma patients. One can also envision 'co-clinical trials' wherein experimental therapeutic trials in the mouse models of glioblastom are linked to analogous small proof-of-concept trials in GBM patients."
Based on material originally posted by Cell Press.