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Glucotoxicity Activates the Growth and Spread of Cancer

Sugar intake seems to promote the growth and spread of tumors in fruit flies through a few pathways….

In the study, Drosophila, also known as fruit flies, are used as a model to examine the effect a diet consisting mainly of sugar has on tumor growth. The fruit flies used in the experiment were genetically engineered to express tumors.

Previous research has shown that a diet high in carbohydrates can lead to metabolic abnormalities such as high blood sugar, increased blood insulin levels, and insulin resistance. Individuals with metabolic diseases such as diabetes and obesity have been shown to have a higher risk of certain cancers, including breast, liver, colon and pancreatic cancers. The link between these metabolic diseases and the risk for cancer has not been clearly understood.

Researchers found that a high intake of sugar "converts Ras/Src-transformed tissue from localized growths to aggressive tumors with emergent metastases." While most tissues presented with insulin resistance, Ras/Src-activated tumors avoided diet related insulin resistance. Therefore, these tumors retained the ability to transport glucose in their cells as well as prevent their own cell death. Ross Cagan, from the Icahn School of Medicine at Mount Sinai in New York City, explains, "The exorbitant glucose levels in the blood pour into the tumor, having nowhere else to go in the insulin-resistant body."

In the fruit flies, high sugar intake also increased the activity of the "Wingless/Wnt pathway," which in turn up-regulated the insulin gene receptor and led to increased insulin sensitivity.

When the flies were given a diet rich in protein but low in carbohydrates, their tumors changed little in size and did not metastasize. The fruit flies were also introduced to a three-drug combination consisting of acarbose, pyrvinium, and an anticancer agent (AD81), which all worked to either decrease blood glucose levels or inhibit the pathways associated to tumor growth/expansion. When given the combination, these drugs helped dramatically reduce the size of the tumors, more so than if they were given individually. Furthermore, the flies had a much longer life span when given the 3-drug combination.

In conclusion, researchers essentially noticed the sugar given to the fruit flies was what fueled the activation of malignant tumors. Cagan et al. believe that in order to treat this diet related tumor growth, a drug intervention affecting the pathways associated with Ras/Src tissues and the insulin gene receptor should be considered. The researchers are currently moving forward to study the effects sugar has on human tumor samples from people with metabolic diseases.

Cagan R, et al. "Transformed Drosophila Cells Evade Diet-Mediated Insulin Resistance Through Wingless Signaling" Cell 2013.