'Smart bomb' delivery destroys tumors in mice
A new method selectively kills cancer cells, leaves healthy ones intact
Rehovot, Israel -- December 29, 2003 -- Weizmann Institute scientists have destroyed malignant tumors in mice using a chemical that occurs naturally in garlic. The key to the scientists' success lies in the development of a unique, two-step system for delivering the cancer-wrecking chemical straight to the tumor cells.
Allicin, as the chemical is called, is the substance that gives garlic its distinctive aroma and flavor. For many years, scientists studying allicin have known that it is as toxic as it is pungent. It has been shown to kill not only cancer cells, but the cells of disease-causing microbes, and even healthy human body cells. Fortunately for our body's cells, allicin is highly unstable, and breaks down quickly once ingested. However, the rapid breakdown and undiscriminating toxicity presented twin hurdles to creating an allicin-based therapy.
At the Weizmann Institute's Biological Chemistry Department, Drs. Aharon Rabinkov, Talia Miron and Marina Mironchick, working with Profs. David Mirelman and Meir Wilchek, have solved both these problems by designing an ingenious delivery method that works with the pinpoint accuracy of a smart bomb. Their findings were reported in the December issue of Molecular Cancer Therapeutics.
The method parallels the way allicin is synthesized in nature. Not present in whole, unbroken cloves of garlic, allicin is the product of a biochemical reaction between two substances stored apart in tiny, adjoining compartments within each clove. The two are an enzyme, alliinase, and a normally inert chemical called alliin. When the clove is damaged, whether by soil parasites intending to eat the tender tissues, or by cooks making sauce, the membranes separating the compartments are ruptured and rapid allicin production follows. The scientists realized that if doses of allicin could be repeatedly generated in this way at the site of the tumor, the highest concentration of the toxic molecules would be available for killing cancer cells.
To zero in on the targeted tumor, scientists took advantage of the fact that most types of cancer cells exhibit distinctive receptors on their surfaces. An antibody that is "programmed" to recognize the tumor's characteristic receptor is chemically bound to the enzyme, alliinase. Injected into the bloodstream, the antibody seeks out these cells, and lodges itself and its passenger enzyme on the tumor cells. The scientists then inject the second component, alliin, at intervals. When it encounters the alliinase, the resulting reaction turns the normally inert alliin molecules into lethal allicin molecules, which penetrate and kill the tumor cells. Due to the precise delivery system, neighboring, healthy cells remain intact.
Using this method, the team succeeded in blocking the growth of gastric tumors in mice. The tumor-inhibiting effects were seen up to the end of the experimental period, long after the internally produced allicin was spent. The scientists note that the method could work for most types of cancer, as long as a specific antibody can be customized to recognize receptors unique to the cancer cells. The technique could prove invaluable for preventing metastasis following surgery. "Even though doctors cannot detect where metastatic cells have migrated and lodged themselves," says Prof. Mirelman, "the antibody-alliinase-alliin combination should chase them down and destroy them anywhere in the body."
Prof. David Mirelman's research is supported by the Y. Leon Benoziyo Institute for Molecular Medicine; Robert Drake, The Netherlands; Mr. and Mrs. Henry Meyer, Wakefield, RI; M.D. Moross Institute for Cancer Research; and The late Claire Reich, Forest Hills, NY. Prof. Mirelman is the incumbent of the Besen-Brender Chair of Microbiology and Parasitology.
The Weizmann Institute of Science in Rehovot, Israel is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,500 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.
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