Retinoic Acid Used In Cancer Treatment

April 13, 1998

ITHACA, N.Y. -- A common chemical derivative of vegetables has been used by Cornell University researchers studying leukemia to block the uncontrolled cell division that leads to cancer.

The chemical is retinoic acid, a product of vitamin A, which the body manufactures from carotenes, the compounds found in a wide assortment of yellow-orange vegetables and fruits, from carrots and sweet potatoes to pumpkins and apricots.

Retinoic acid reverses the growth-promoting effects of oncogenes, the mutated genetic material that induces cancer, says Andrew Yen, a professor of pathology and director of one of the Cancer Biology Laboratories in Cornell University's College of Veterinary Medicine.

The finding, which to date has been restricted to the test-tube level, could lead to enhanced therapies for those cancers, including leukemia, that seem to respond to retinoic acid. The research also highlights the cancer-prevention role of carotenes.

"This is one more reason," Yen says, "to listen to your mother and eat your vegetables."

Yen reported the cell growth-arresting function of retinoic acid March 30 in New Orleans at the annual meeting of the American Association for Cancer Research. More details are in an article prepared for the association's journal, Cancer Research. Previously, progress by Yen's laboratory in explaining the role of retinoic acid was reported in a series of articles in several journals, including Blood, European Journal of Cell Biology and Experimental Cell Research.

Retinoic acid is a metabolic product of retinol, the active form of vitamin A. The compound had been shown by other researchers to regulate normal cell growth and differentiation. Yen's latest results -- using transforming proteins to switch on proto-oncogenes, the precursors to oncogenes -- demonstrate how retinoic acid can use the same chemical-signalling cascades that cause cell growth instead to arrest growth.

"Retinoic acid can reverse the defect in growth control that was caused by the viral agent and result in cell-growth arrest," Yen says, describing his experiments with cell cultures. "Now we need a deeper understanding of how retinoic acid causes these changes -- and exactly which molecules are affected by retinoic acid. In my dreams there is a single effector, but it's more likely there are several."

Ongoing studies in the Yen laboratory, supported in part by the National Cancer Institute and the U.S. Department of Agriculture's Program in Human Nutrition, aim to explain exactly how retinoic acid works on oncogenes and whether other, related compounds would be more effective in chemotherapy. As a result, oncologists might be able to fine-tune the chemotherapy cocktails given not only to leukemia patients but also to patients with other types of cancer, Yen suggests.

"In the meantime," he says, "I think we're adding evidence that an adequate supply of carotene in the diet is obviously beneficial for anyone who wishes to stay healthy and avoid cancer."

Cornell University

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