In my Cell Biology class we recently had a discussion about a scientific paper called: Phosphorylation of Mcl-1 by CDK1–cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest. That’s quite a mouthful, and as a scientific paper it’s pretty complex and difficult for the average person, but it offers and explanation for how many chemotherapy drugs which are used to treat cancer are actually able to kill the cancer cells. That may sound pretty basic, but we have actually been using these drugs without really understanding how they kill cells. We have known that these drugs (including Taxol, Nocadazole, Vinblastine, and Vincristine) limit the normally dynamic nature of microtubules, which are usually constantly breaking down and rebuilding in different ways to allow changes in the cell, but didn’t know why this made cells die.
The rearrangement of microtubules, which act as a form of structural support within the cell, is most important and dynamic during mitosis (cellular replication) when the microtubules help ensure that the DNA is separated properly between the two new cells. The picture above shows how microtubules (green) have to rearrange in the different stages of cell division (going from a to f) to properly separate the DNA (blue). When dividing cells are treated with these chemo drugs, their microtubules aren’t able to rearrange and help the chromosomes align and separate properly and they get stuck in mitosis. Scientists knew that this happened, but not how that would cause the cells to die.
This paper identified a protein (Mcl-1) which acts as a timer during cell division, if the cell takes too long to divide the protein signals the cell to die. Mitosis was not thought of as a timed process, it continues for as long as it takes until the DNA is properly divided and the two new cells separate. This shows that when something goes wrong and the cell becomes stuck, like when treated with these types of chemo drugs, it will go through a controlled death process. Since cancer cells are dividing at a much higher rate than normal, healthy cells, mostly cancer cells are affected.