HOUSTON - Researchers at The University of Texas M. D. Anderson Cancer Center have significantly refined the scientific understanding of how a cell begins the process of self-destruction - an advance they say may help in the design of more targeted cancer therapies.
In the June 30 issue of the journal Cell, the research team found that a natural "brake" exists in a cell to prevent it from undergoing apoptosis, or programmed cell death, and they say that optimal anti-cancer therapies should take a two-pronged approach to overriding this brake in order to force a tumor cell to die. Very few drugs do this now, they say.
The discovery "demonstrates that apoptosis is more complicated than had been believed, and consequently harder to achieve," says the study's lead author, Dean G. Tang, Ph.D., associate professor in the Department of Carcinogenesis in the Science Park Research Division of M. D. Anderson in Smithville, Texas.
Apoptosis can occur when a cell has reached its lifespan, and so is "programmed" to die, or is initiated when a cell is damaged beyond repair or infected by a virus. Apoptosis is rare in cancer because tumor cells have adapted biological pathways to circumvent cell death, so many anti-cancer therapies focus on inducing apoptosis in these cells, Tang says.
But the notion of how to push cancer cells to die has been flawed, Tang says. These new findings "overturn a scientific dogma so long accepted that it has become a textbook standard when talking about apoptosis," he continues.
Researchers agree that the seminal event that leads to initiation of apoptosis is the release of a key protein known as cytochrome c (CC) from a cell's mitochondria, the organelle's energy storehouse. These molecules then bind to another protein called Apaf-1 in the cell cytoplasm, and together they form a scaffolding "death wheel" to activate enzymes called caspases that shred a cell apart.