Inhibiting Glycolytic Respiration Stops Tumor Growth

Cancer researchers have described a mechanism that explains how cells buried in the center of tumors and virtually cut off from sources of oxygen manage to survive and replicate.

Investigators at Harvard Medical School (Boston, MA, USA) capitalized on the latest genetic engineering techniques to study the anaerobic glycolytic pathway in tumor cells. They used short hairpin RNAs to knock down the level of lactate dehydrogenase A (LDH-A) in a line of fast-growing breast cancer cells, which effectively prevented the cells from metabolizing pyruvate to lactate. The modified tumor cells were implanted into a group of mice while a control group received untreated cells.

Results published in the June 2006 issue of Cancer Cell revealed that while all the mice in the control group died from cancer within 10 weeks, more than 80% of the animals in the test group survived to the end of the four-month experiment.

Reduction in LDH-A activity forced the cells to rely on oxidative phosphorylation, which was characterized by stimulation of mitochondrial respiration and decrease of mitochondrial membrane potential. When the tumors became too large, the cells at the center were unable to breathe and died off.

"The findings provide us with an insight into a mechanism that had been suspected in the last six or seven decades,” said senior author Dr. Philip Leder, professor of genetics at Harvard Medical School.

The investigators suggested that coupling treatment to prevent glycolysis with drugs to inhibit synthesis of new blood vessels might prove to be an effective anti-cancer regime.



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