Finding Chinks in the Armor: Cancer’s Need for Metabolites

Illustration of energy metablism in cell.

Cancer has been studied for decades by scientists trying to find a vulnerability to exploit and testing compounds to develop as potential drugs. As the “Emperor of All Maladies”, cancer has proven itself to be a wily beast with many varieties of genetic mutations for eluding cellular control, tireless in its ability to divide and spread. In the end, a cancer cell is still a cell and subject to its environment even though cancer does not play by the same rules as the normal cells that exist around it. To be able to grow, a cell needs access to metabolites, molecules needed for building the materials and machinery needed by the cell to function and divide. These requirements also offer potential pathways to target for halting cancer growth and spread.

All cells use glucose to generate ATP, but normal and cancer cells differ in how glucose is converted to ATP. Most cells use glucose in oxidative phosphorylation, but cancer cells use aerobic glycolysis, converting glucose to lactate without oxygen. This Warburg effect (glucose converted to lactate) is a hallmark of cancer cells as they take up glucose at a much higher rate than normal cells. Blocking glucose uptake is one way to target cancer cells. While 2-deoxyglucose (2DG) has been shown to slow glucose uptake in vitro, the compound proved toxic in clinical trials and lower dosages do not seem to be an effective treatment against cancer. While not an ideal drug target, glucose uptake has been helpful in monitoring cancer response to therapies via fluorodeoxyglucose positron emission tomography (FDG-PET).

Continue reading “Finding Chinks in the Armor: Cancer’s Need for Metabolites”

Developing a Model System to Test Ketamine Toxicity

Figure 2. Ketamine induced morphological changes in neurons derived from iPSCs. Cells were treated with 0μM (Panel A), 20μM (Panel B), 100μM (Panel C) or 500μM (Panel D) ketamine for 24 hours. doi:10.1371/journal.pone.0128445.g002
Ketamine induced morphological changes in neurons derived from iPSCs.
Cells were treated with 0μM (Panel A), 20μM (Panel B), 100μM (Panel C) or 500μM (Panel D) ketamine for 24 hours. Scale bar = 50μm. From Ito, H., Uchida, T. and Makita, K. (2015) Ketamine causes mitochondrial dysfunction in human induced pluripotent stem cell-derived neurons. PLOS ONE 10, e0128445.
When I consider that major surgery was performed long before anesthetics were developed, I am grateful to be alive in the anesthesia era. Just the thought of being subjected to various cutting and retracting instruments without general anesthesia calls to mind a phrase: The cure is worse than the disease. Despite the advantages of unconsciousness during surgery, anesthesia can have side effects. Studies in neonatal nonhuman primates have demonstrated that the anesthetic ketamine has toxic effects. However, the differences between humans and nonhuman primates mean the outcome in one species is not the same in another. In an article recently published in PLOS ONE, scientists were interested in creating an experimental model of developing human neurons and using the model to better understand the toxic effects of ketamine on human cells. Continue reading “Developing a Model System to Test Ketamine Toxicity”

A New Role for Reactive Oxygen Species: Can We be Aged and Thin?

Add pomegranite to the list of so-called superfoods.

Since the 1980s, we’ve been told that aging can be accelerated by a build-up of free radicals in our cells. We’ve learned that to counteract the damage that free radicals (or reactive oxygen species, ROS) can wreak on our bodies, we should consume  antioxidants like vitamins C and E, and phytochemicals.

In fact, the term “superfood” was coined for foods that contain high levels of antioxidants, phytochemicals and vitamins, foods like blueberries and carrots, spinach and kale, to name a few.

 “Hold the phone”, as a pre-calculus professor of mine used to say.  Turn off the blender and put down that shot glass of beet-carrot-lemon grass juice. This research just in: “Free Radicals Crucial to Suppressing Appetite”.

The research was published August 28, 2011 in the advanced online edition of Nature Medicine.

In this study, Yale University researchers reported that elevated levels of ROS  in the brain activated satiety-generating neurons. Continue reading “A New Role for Reactive Oxygen Species: Can We be Aged and Thin?”