It has been noted that when Cancer cells are treated with a
particular dose of drug, some cells die while the other survive. For instance, on
treating with IC-50 of a drug, 50% of cancer cells die while other 50% survive.
Deputy director of the University of Colorado Cancer Center, Andrew Thorburn,
PhD, answers this question in his new
journal published in Nature Cell Biology: it is due to the variations in random
autophagy in cells.
Autophagy is a process through which cell survives under the unfavourable
conditions such as stress or deficiency by breaking down its non necessary
components to provide energy to be used in degrading potentially harmful
proteins. Hence, preventing any cellular damage. Thus cancer cells having low
autophagy are more prone to death when treated with anti-cancer drugs than
those that have low mortality due to high extent of autophagy. In his current
study, Dr Andrew Thorburn shows that extent of autophagy and particular mechanism
of anti-cancer drug are the two factors that influences the rates of cell
death, either increasing or decreasing it.
According to Thorburn, cancer cells were separated into two
different populations on the basis low and high autophagy respectively. These
two populations were treated with death activating two drugs . On the action of
first drug, cells with high autophagy had the highest mortality, while on
treatment with the second drug, cells with low autophagy had the highest
mortality. Thus, effect of autophagy was opposite depending on the drug.
Thorburn and his colleagues including Jacob Gump, PhD ,
treated both cell populations, low and high autophagy with two chemicals TRAIL
and Fas ligand, which activate cells' death receptors. Cells treated with these
chemicals die . Hence, some cells in both the populations underwent programmed
cell death called apoptosis. It was observed that cells in population with high
autophagy were more sensitive to chemical Fas ligand while cells in population
with low autophagy were more sensitive to chemical TRAIL. Even in cancer cells,
similar observations were noted as autophagy protects against these drugs in
some cancer while in some , autophagy makes it more vulnerable.
In certain cancer cells, some but not all, a protein called
FAP-1 is present whose major function is to prevent cell death by action of Fas
Ligand. Groups showed that Autophagy degrades this FAP-1 protein when present
in cells, making them more vulnerable to cell death by action of Fas ligand.
Hence, how autophagy causes cell death in some tumors when treated with certain
drugs is explained but not how it helps survival of other category of cells.
Moreover,
Thorburn pointed out that cells in lab studies tend to be homogenous in their
levels of autophagy compared to cells in natural tumor environments. It is
likely, these laboratory results will be magnified in actual tumors, where
levels of autophagy tend to vary more broadly.
While
Fas ligand and TRAIL agonists are used in the lab only at this time. He further
states that in future, further research will be done by performing similar experiments with drugs that could be
used in people.
