>> NARRATOR: In the following films, we see
two identical cultures of cancer cells followed
in time lapse under the microscope.
The culture on the right is an untreated control,
while TTFields are being applied continuously
to the culture on the left.
The first difference between the cultures
appears about two hours after treatment start
- no cell divisions are seen in the TTFields
treated culture, whereas in the control culture,
cells have already started to divide.
It takes 12 hours for the first cell to round
up for mitosis in the treated culture.
In addition, cell cleavage (cytokinesis) is
delayed and takes three hours to finish.
The next difference in the cultures is that,
in the treated culture, cells round up
for mitosis.
However, they are not able to complete the
normal division process at all.
They remain arrested in mitosis for about
five hours and then die through programmed
cell death (apoptosis).
This mitotic arrest and apoptosis is seen
in dividing cells only.
The dying cancer cells in the TTFields-treated
culture exhibit membrane blebbing, the hallmark
morphologic characteristic of programmed cell
death, also known as apoptosis.
After almost two days of TTFields treatment,
the difference between the control and treated
cultures is clear: Cancer cells fill the entire
available space in the control culture, while
in the TTFields treated culture, only those
cells that did not attempt to divide remain alive.
Cells undergoing apoptosis are also known
to bind annexin to the plasma membrane.
The red color seen in these pictures shows
annexin bound to the membrane of the cancer
cells treated by TTFields.
These cells subsequently undergo apoptosis.
One of the primary structures influenced by
TTFields is the spindle protein, tubulin.
By using tubulin fused to a green fluorescent
protein, it is possible to follow spindle
morphology during cancer cell replication.
As seen in this time-lapse microscopy film,
TTFields application to cancer cells leads
to abnormal spindle formation and, eventually,
to apoptosis.
