Synthetic molecules hold promise as anti-cancer drugs

The man-made fat molecules would selectively induce apoptosis (programmed cell death) only in tumorous cells while inducing fewer side effects than current drugs.

By JUDY SIEGEL-ITZKOVICH
cancer cell 88 (photo credit: )
cancer cell 88
(photo credit: )
Man-made fat molecules injected into mice have reduced the size of pancreatic, prostate and breast tumors with little or no effect on normal cells. If they work as well in humans, researchers at the Hebrew University's biochemistry department and the HU-Hadassah Medical School foresee the development of a new generation of anti-cancer drugs that would selectively induce apoptosis (programmed cell death) only in tumorous cells while inducing fewer side effects than current drugs. For their work in developing these harbingers of a possible new generation of anti-cancer drugs, Dr. Arie Dagan and Prof. Shimon Gatt received the Kaye Award for Innovation on June 4 during the 71st meeting of the HU's board of governors. The artificial molecules affected the metabolism of various sphingolipids - a family of complex lipid molecules involved in mediating cell growth, differentiation and death. Several of the most active molecules developed by Dagan and Gatt are derivatives of ceramide (a member of the sphingolipid family), which induces programmed cell death in a variety of cancer cells. The natural levels of ceramide in such cells are generally too low to have a therapeutic effect. In preclinical studies so far, various treatments with the synthetic molecules resulted in an elevation of ceramide levels in cancer cells, leading to their death by apoptosis. In addition, these synthetic molecules appear to be synergistic with chemotherapeutic drugs. Their discovery has been patented by Yissum (the HU's technology transfer company), and licensed to BioLineRx, a clinical-stage development company traded on the Tel Aviv Stock Exchange. The Kaye Innovation Awards have been given annually since 1994. Isaac Kaye of England, a prominent pharmaceutical industrialist, established the awards to encourage HU faculty, staff and students to develop methods and inventions which benefit society. SHEBA HOSPICE GETS REPRIEVE The 18-bed hospice at Sheba Medical Center has won a reprieve. One of only two hospital-based facilities for the terminally ill (aside from that at Hadassah University Medical Center on Mount Scopus in Jerusalem), it was threatened with "death" by the end of June by the Finance Ministry and lack of action by the Health Ministry. A petition from patients and supporters is being signed via the Internet, and the Israel Cancer Association (ICA) has sent a letter of protest to Prime Minister Ehud Olmert. The problem did not involve funding but bureaucracy and the lack of job slots for hospice employees. Health funds pay the hospice to care for dying members, but there are no official job slots for the palliative medical institution's 30 workers, who come from Sheba. After the Civil Service Commission decided that the hospice must have official job slots for its staffers, the Treasury was approached by the Health Ministry, which finally agreed to help out. However, the Finance Ministry's budgets division pulled out of the compromise. The hospice was established just outside the hospital 25 years ago by the ICA and Clalit Health Service, and its staffers were financed by the ICA until 10 years ago, when Sheba took over responsibility. It has provided palliative care and emotional support for 10,000 terminally ill patients and their families since then. But now, after a public protest, the Treasury has reached a compromise with the patients' lobby and Sheba and added manpower slots as needed. Sheba also contributed its share to the agreement. AN APPLE PEEL A DAY COULD KEEP CANCER AT BAY Apple peels are good for you and could prevent cancer, according to food science Prof. Rui Hai Liu of Cornell University, who has identified a dozen compounds called triterpenoids in apple peels that either inhibit or kill cancer cells in the lab. Three of the compounds had never been described in the literature. "We found that several compounds have potent anti-proliferative activities against human liver, colon and breast cancer cells and may be partially responsible for the anti-cancer activities of whole apples," writes Liu, senior author of the study published in the Journal of Agricultural and Food Chemistry. In previous Cornell studies, apples had been found not only to fight cancer cells in the lab but also to reduce the number and size of mammary tumors in rats; now the Cornell researchers think it may be triterpenoids that do much of the anti-cancer work. "Some compounds were more potent and acted differently against the various cancer cell lines, but they all show potent anti-cancer activity and should be studied further," said Liu. He and colleagues analyzed the peel from 230 pounds of red Delicious apples from the Cornell orchard and isolated their individual compounds. After identifying the structures of the promising compounds, they tested the pure forms against cancer cell growth in the lab. In the past, Liu has identified compounds called phytochemicals - mainly flavonoids and phenolic acids - in apples and other foods that also appear to have anti-cancer properties, including inhibiting tumor growth in human breast cancer cells. "We believe that a recommendation to eat five to 12 servings of a wide variety of fruits and vegetables daily is appropriate to reduce the risk of chronic diseases such as cancer, and meet nutrient requirements for optimum health," said Liu.