Autophagy inhibition proves to fight cancer

Have you ever seen Breaking Bad? If not, here’s the premise: Man finds out he has cancer. Man cannot pay for cancer and does not want to leave his family in debt if he is going to die. Man turns to making crystal meth to make big cash. It’s a slippery slope from there.

What if I were to tell you that there was a surefire way to ensure his survival? What if I told you that this cure was for him to eat himself? It turns out that this is the case, except not for our benefit.

A recent study released by the University of Colorado Cancer Center shows that some cancer cells can bring themselves back from death by ingesting themselves.When under times of extreme stress cells undergo autophagy, a word of Greek origin, which means “to eat oneself.” In this process, the cells produce autophagosomes which isolate potentially harmful substances and bring them to lysosomes. At the lysosome, the substance is broken down to material that can be saved for future use.

For example, when mitochondrial walls break down, the cell begins the releasing proteins in a process referred to as MOMP. From here, the cell begins to produce p53 Unregulated Modulator of Apoptosis, or PUMA, which increases the apoptotic rate of the cell. PUMA can control the rate of autophagy; in the presence of excess PUMA, the cell will undergo apoptosis rather than eating the apoptotic proteins.

However, if the level of autophagy is high enough, the cell can digest the MOMP proteins before they can produce PUMA, thus saving it from death’s grip.

It turns out that cancer cells do this. To prove this, the researchers exposed the chemotherapy drug TRIAL to cancerous cells in which PUMA was removed.

Because PUMA was not around to regulate the rate of autophagy, the cells were able to “eat” enough of its own material to generate new cellular organelles and proteins. Through this process the cancerous cell was able to produce a “new cell” that had its cellular function and reproduction capability completely restored.

Autophagy is naturally induced in many instances, including during physical exercise. In a study released in 2012, Dr. Beth Levine and a team of researchers at the University of Texas Southwestern Medical Center discovered that mice with high rates of autophagy were able to sustain a longer time period of physical exercise. Next, they fed the mice a high-fat diet, which led to diabetes in the mice. After 8 weeks, mice with high levels of autophagy related to increased exercise were able to reverse their diabetes. Other previous studies have indicated that sustained physical activity increases the basal rate of autophagy, which leads to heightened mitochondria and muscular biogenesis.

This study emphasizes the necessity to inhibit autophagy in the treatment of cancers. With more research into this area, drugs that inhibit autophagy may be discovered and the success of cancer therapies may increase.