Chances are you already know that eating too much sugar isn’t good for you. Yet you’re probably still overdoing it. Americans average about 270 calories of sugar each day. That’s about 17 teaspoons a day, compared to the recommended limits of about 12 teaspoons per day or 200 calories. However, researchers from USC Viterbi’s Mork Family Department of Chemical Engineering and Materials Science have unlocked a weakness in a common type of cancer cell: sugar inflexibility. This means that when cancer cells are exposed to a different type of sugar, galactose, the cells can’t adapt and will die.
New metabolic treatments
The discovery, which could have important implications for new metabolic treatments for cancer, was led by Dongqing Zheng, a Ph.D. student in the lab of Nicholas Graham, assistant professor of chemical engineering and materials science. The research was recently published in the Journal of Cell Science.
Underlying the research are the following ideas: The uncontrolled cellular growth that characterizes tumor formation requires a constant delivery of nutrients and, like any cells in the body, cancer cells need sugar, namely glucose, to fuel cell proliferation and growth. Cancer cells in particular metabolize glucose at a much higher rate than normal cells. The researchers are taking a systems biology approach to try to understand ways in which to shrink cancer tumors without the side effects of chemotherapy and radiation. Zheng said that galactose is quite structurally similar to the glucose which helps cancer cells thrive, but that it has some differences.
The paper describes how oncogenes, the genes that cause cancer, can also cause cancer cells to become inflexible to changes in their sugar supply. Normally, cells grow by metabolizing glucose, but most normal cells can also grow using galactose. However, the team discovered that cells possessing a common cancer causing gene named AKT cannot process galactose, and they die when exposed to this type of sugar. Galactose is a simple sugar, which belongs to the class of simple carbohydrates. Galactose is composed of the same elements as glucose but has a different arrangement of atoms.
Graham said that exposing cells to galactose forces them to do more oxidative metabolism, where oxygen is used to convert sugars into energy, unlike glycolytic metabolism, where energy is derived from glucose. Normal cells can metabolize both glucose and galactose, but cancer cells with an activated AKT signaling pathway, commonly found in breast cancer cells, cannot.
The team’s findings
Graham said that they “hadn’t seen research looking at galactose in a cancer context, to see whether specific mutations can cause cancer cells to be better or worse at managing that switch between glycolytic and oxidative metabolism.”
Zheng said that the discovery did not mean that galactose itself would be an effective treatment for AKT-type cancer cells, but that it did uncover a fundamental flaw in these cells, whereby the oxidative state leads to cell death.
The team’s findings also showed that while the oxidative process that is initiated by galactose did result in cell death in AKT-type cancer cells, when the cells were given a different genetic mutation, MYC, the galactose did not kill the cells. “So if you had a drug that could inhibit glycolysis, you would give it to a patient that had an AKT mutation,” Graham said. “But you wouldn’t give it to a patient that had an MYC mutation, because it wouldn’t work theoretically for those MYC cells.”
The researchers also discovered that, after around 15 days in galactose, some cancer cells started to reoccur. Zheng responded to this result saying that “Maybe there is a small sub population that are resistant to the galactose. The other possibility is that some cancer cells are very resilient and they adapt and reprogram themselves after two weeks exposed to the galactose treatment.”
The systems biology approach to cancer treatment is different than traditional treatments like chemotherapy and radiation therapy in that it targets metabolic processes in cancer cells. It aims to identify drugs without a lot of the side effects of traditional chemotherapies that also kill healthy cells, leading to adverse effects such as hair loss. However some resurgence is common in a lot of targeted metabolic treatments for cancer, which demonstrate strong initial results before a partial recurrence of the cells. Graham said that AKT tumors can potentially be targeted using a metabolic treatment like this in order to initially shrink the tumor, but that the treatment would need to be accompanied by another treatment in a drug cocktail to prevent recurrence and to protect against cancer cells adapting and mutating.
Sparking hope and positivity in cancer research
“What we’re trying to do is to use a systems approach to understand this, so we can use some type of targeted drug or gene therapy that can induce a similar effect and force the cell into this oxidative state,” Zheng said. Further research is necessary, but this initial research certainly sparks hope and positivity in the progress of cancer research and treatment.
References
- A sugar hit to help destroy cancer cells
- How Much Sugar Do You Eat? You May Be Surprised!
- AKT but not MYC promotes reactive oxygen species-mediated cell death in oxidative culture | Journal of Cell Science | The Company of Biologists
- Dietary Fat and Sugar in Promoting Cancer Development and Progression | Annual Review of Cancer Biology
- What is galactose? Definition, Foods, Metabolism
- A Monosaccharide Glucose: Foods, Absorption, Function, Health Effects
