Starving Cancer of Glucose and Glutamine. Better Aging Series Part 8

In the latest of my posts on better aging, I’m going to discuss the topic of starving cancer cells. Biologists have known for nearly a century that some types of cancer cells consume significantly more glucose than normal cells. Healthy cells burn most of a sugar molecule in their mitochondria in order to make energy, which is why mitochondria are often referred to as cellular “power plants.”

A new paper in the journal Cell Metabolism attempts to address this question. In doing so, authors Craig Thompson and Natasha Pavlova launch a novel explanation for the origin of cancer itself.

One of the great fundamental challenges of biology is how multicellular organisms evolved, and how these clusters of cells manage to function together harmoniously. Dr. Thompson has argued that the cells that make up multicellular organisms operate in a fundamentally different way than their single-celled counterparts. This union of cells works because the individual cells in the group operate according to certain “rules,” which ensure that they share nutritional resources and only take up nutrients in response to growth signals. In contrast, single-celled organisms are able to consume nutrients continuously, without regard for cells around them, and can reproduce relatively freely.

Due to the effects of mutations, cancer cells essentially become “antisocial” – they are able to deviate from the rules, without regard for how it affects the wellbeing of the whole. Instead of behaving cooperatively, as part of a larger organism, a cancer cell feeds and reproduces itself without inhibition. The authors liken the nutrient uptake of cancer cells to yeast blooming in a vat of sugar. Cancer cells behave more like a single-celled organism, governed by its own interests, rather than as a part of a greater cellular “community.” This metabolic shift results in aberrant tissue growth, detrimental to the whole organism. It is this altered metabolism of nutrients, according to the authors, that is cancer’s true cause.

In fact, it appears that cancer cells may derive energy by literally consuming cellular signals. Zhao and colleagues came upon this discovery when investigating the role of exosomes, which are tiny pouches of proteins and nucleic acids that transmit information between cells. The team was surprised to find that not only were the cancer cells receiving these signals from other cells, they were using them as a source of energy, consuming amino acids directly from the exosomes. This is another example of how remarkably resourceful cancer cells can be – drawing in glucose and amino acids from the environment as building blocks for tumors.

Why should all of this matter to us? Recognizing the fundamental importance of metabolic alterations could have major implications for cancer treatment. In their article, Thompson and Pavlova identify six distinct areas of cell-metabolite interaction, all of which become dysregulated in cancer cell metabolism. Any of these could emerge as potential therapeutic targets.

For example, drugs that are known to affect cell-signaling pathways but that have not traditionally been associated with cancer treatment, such as metformin, may prove to be effective cancer-suppressing therapies. Metformin is commonly prescribed for diabetes due to its effects on metabolic and intracellular-signaling pathways. It inhibits glucose production from the liver, and reduces levels of insulin in the bloodstream. This reduction in insulin stimulation results in less activation of insulin receptors. In turn, this leads to the downregulation of certain signaling pathways that are associated with cell growth and proliferation – and which are commonly used by cancer cells. To recall a line from a previous post on aging, I wrote: “there are more than 200 ongoing clinical trials studying the effect of metformin in preventing and even treating cancers.”

Furthermore, as we continue to better understand how cancer cells acquire access to and utilize nutrients, we may also be better able to understand dietary therapies that have been investigated for treatment or prevention of cancer. For example, adherence to a ketogenic diet may help “starve” cancer cells by depriving them of glucose for energy. Taking this information together, a low glutamine ketogenic diet might prove to be quite useful to certain types of cancers.

The Warburg model may also shed light on why many nutritional supplement interventions, which initially seemed so promising, have ultimately proved to be disappointing (or even outright harmful). In the next blog post on this subject, we will discuss one such example.