Why Sugar Starvation Kills Some Cancer Cells

Starving cancer cells of sugar under conditions of elevated calcium can result in cancer cell death, scientists say.

AsianScientist (Feb. 1, 2018) – Scientists in Singapore and Austria have identified the mechanism by which sugar starvation causes cancer cells to die. They published their findings in Science Signaling.

Previous research has shown that rapidly dividing cancer cells require higher levels of sugar than healthy cells. This dependency on sugar distinguishes cancer cells from normal cells and is often used as a treatment option to kill cancer cells.

In reality, however, the results have not been encouraging. Not all cancer cell types are sensitive to the removal of sugar, and even for the cancers that are sensitive, sugar depletion only slows down the rate of cancer progression. The pathways that sensitize cancer cells to sugar deprivation remains poorly understood.

In a study led by Associate Professor Koji Itahana of the Duke-National University of Singapore Medical School, together with a team of collaborators led by Dr. Egon Ogris of the Max F. Perutz Laboratories in Austria, scientists have demonstrated how sugar deprivation results in cancer cell death.

The team discovered that in some cancer cells, low levels of sugar that were incapable of providing sufficient energy ended up enhancing the survival of the cancer cells. This suggested that in addition to providing energy, sugar has a pro-survival function.

The researchers subsequently found that sugar deprivation triggers voltage differences across the cancer cell membrane, leading to an influx of calcium ions into the cells, which causes cell death. They speculated that this unique property of sugar in cancer cells could be manipulated for cancer therapy.

By combining the inhibition of sugar intake and the increase of calcium levels in cancer cells, they managed to kill cancer cells while leaving healthy cells intact. Itahana and colleagues also found that certain cancer cells lost the ability to sustain intracellular sugar levels after sugar deprivation, which may help explain why not all cancer cells are sensitive to sugar deprivation. The team aims to further their research to develop a new cancer treatment in the future.

The article can be found at: Lee et al. (2017) Ca2+-dependent Demethylation of Phosphatase PP2Ac Promotes Glucose Deprivation–induced Cell Death Independently of Inhibiting Glycolysis.


Source: Duke–NUS Medical School; Photo: Shutterstock.
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