Hybrid molecule causes cancer cells to self-destruct

By joining a sugar to a short-chain fatty acid compound, Johns Hopkins researchers have developed a two-pronged molecular weapon that kills cancer cells in lab tests. The researchers cautioned that their double-punch molecule, described in the December issue of the journal Chemistry & Biology, has not yet been tested on animals or humans. Nevertheless, they believe it represents a promising new strategy for fighting the deadly disease.

"For a long time, cancer researchers did not pay much attention to the use of sugars in fighting cancer," said Gopalan Sampathkumar, a postdoctoral fellow in the university's Department of Biomedical Engineering and lead author of the journal article. "But we found that when the right sugar is matched with the right chemical partner, it can deliver a powerful double-whammy against cancer cells."

Sampathkumar and his colleagues built upon 20-year-old findings that a short-chain fatty acid called butyrate can slow the spread of cancer cells. In the 1980s, researchers discovered that butyrate, which is formed naturally at high levels in the digestive system by symbiotic bacteria that feed on fiber, can restore healthy cell functioning.

Efforts to use butyrate as a general drug for tumors elsewhere in the body, however, have been hindered by the high doses of the compound needed to effectively eradicate cancer. To get around this problem, scientists have tried to make butyrate more potent by modifying it or joining it to other compounds. Usually, the results have been disappointing because the molecular partner added to butyrate to improve delivery to the cancer cells often produced unsafe side effects.

In some of the less successful experiments, designed to avoid toxic side effects, researchers used innocuous sugar molecules such as glucose to carry butyrate into the cells. The Johns Hopkins team tried a different tack. "We didn't think they chose the right partner molecule," said Kevin J. Ya

Contact: Phil Sneiderman
Johns Hopkins University

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