Synthetic Cell-Signaling Molecule Fights Cancer

The studies were funded by the U.S. National Cancer Institute.

"Many agents suppress cancer cells in a petri dish and then not in the whole animal, or have unacceptably high toxicity for normal tissues,” said Dr. Al Merrill, a professor of biology at Georgia Tech. "Finding that enigmols are effective in three animal models leads us to hope these may be a new approach to treat cancer.” Human studies, however, still need to be performed to establish efficacy and safety in humans, cautioned the researchers.

Enigmols are synthetic analogs of sphingolipids, a group of cell-signaling molecules that help cells choose to whether to grow or die by way of a controlled mechanism called apoptosis. Cancer cells are typically defective in these regulatory pathways, therefore scientists theorized that structurally engineered sphingolipid analogs might even be better at making cancer cells behave more normally.

The researchers found that sphingolipids, found in some foods, including soybeans and low-fat dairy products, suppress tumors in mouse models for colon cancer. Encouraged by these findings, scientists at Emory University prepared nearly 100 sphingolipid-based analogs that led to the discovery that enigmols are the most effective tumor suppressors. Emory University holds the patent on enigmols.

In addition to being more potent than naturally occurring sphingolipids, the investigators also discovered that enigmols can be given orally, and appear frequently in difficult-to-reach organs, including the prostate. "This is what suggested to us that enigmols should be tested against other cancer types,” Dr. Merrill explained.

The scientists then discovered that enigmols block the growth of human prostate tumors implanted in lab mice. They were also effective in two other mouse models for colon cancer. "We do not know why enigmols affect such a wide range of tumor cell types,” Dr. Merrill said. "But it may be due to the involvement of sphingolipids in multiple cell-signaling pathways. This means a compound may affect several different targets, rather than just one.”

In fact, enigmols may act like a multi-drug combination therapy, the researchers hypothesize. These compounds are also being used in combination with other chemotherapeutic agents. "Even if enigmols are effective in humans, the greatest success is likely to come from the right combination of drugs that interact in a synergistic way,” Dr. Merrill noted.



Related Links:
Georgia Institute of Technology
Emory University
Wayne State University