Itraconazole (Sporanox® | Janssen pharmaceutica), an antifungal drug commonly used against toenail infections, can also inhibit the proliferation of blood vessels in tumors. This was revealead in a new research article published in the April 2007 issue of American Chemical Society’s Chemical Biology. To identify antiangiogenic agents, Chnog and his team screened a library of FDA approved inhibitors of human endothelial cell proliferation using human umbilical cord cell lines, and identified itraconazole as a potential drug for preventing angiogenesis.
The study conducted by the same scientists in mice induced for excess blood vessel growth showed that itraconazole treatment reduced the proliferation of blood vessels by 67% compared to placebo. They also identified human lanosterol 14α-demethylase (14DM), which is partially inhibited by itraconazole, as a novel therapeutic target for angiogenesis inhibition.
Angiogenesis is a physiological process in the body that involves the growth of new blood vessels from pre-existing blood vessels. It is a normal process in growth and wound healing. However, it is also an essential step in the transition of dormant cells to malignant tumor cells. The new blood vessels provide nutrients and oxygen essential for the growth of tumor cells.
Scientists have been trying since many years to find a potent drug that can inhibit or prevent tumor-related angiogenesis. Poon et al in 2003 reported antiangiogenic therapy as a promising therapeutic strategy for gastrointestinal cancers. Aozuka et al in 2004 studied the efficacy of bestatin against B16-BL6 melanoma cells, and recommended bestatin as a potent drug that can inhibit invivo tumor angiogenesis.
Itraconazole, a synthetic triazole agent with antimycotic activity, acts by inhibiting the fungal cytochrome p450 oxidase, the key enzyme involved in the synthesis of fungal ergosterol. Although the researchers found that the drug possibly acts on the same enzyme to prevent formation of new blood vessels, the exact mechanism of action remains unknown.
About Janssen – Janssen pharmaceutica is a Belgium based pharmaceutical company focused on conducting research and development for a wide range of human diseases, including neurological disorders, gastrointestinal disorders, fungal infection, allergies, and cancer. In 1961, the company merged with Johnson & Johnson, a New Jersey based multinational company. In 1995, Ortho-McNeil Inc merged with Janssen pharmaceutica to form Janssen-Ortho Inc, an innovative research based pharmaceutical company. Janssen-Ortho Inc focuses on key therapeutic areas such as mental illness, women’s health, oncology, nephrology, infectious diseases, gastroenterology, wound healing, and erectile dysfunction. Ortho-McNeil Pharmaceutical, a subsidiary of Johnson & Johnson and PriCara, another unit of Ortho-McNeil, develops therapeutics and resources in the areas of pain, gastrointestinal disorders, and infectious diseases.
References
1. Chong CR, Xu J, Lu J, et al.Inhibition of Angiogenesis by the Antifungal Drug Itraconazole. J. ACS Chem Biol. April 20, 2007; 2 (4), 263–270.
2. Poon RT, Fan ST, Wong J, et al. Clinical significance of angiogenesis in gastrointestinal cancers: a target for novel prognostic and therapeutic approaches. J.Ann Surg. 2003 Jul; 238(1): 9-28.
3. Aozuka Y, Koizumi K, Saitoh Y, et al. Anti-tumor angiogenesis effect of aminopeptidase inhibitor bestatin against B16-BL6 melanoma cells orthotopically implanted into syngeneic mice. J. Cancer letters. 2004 December;216(1):35-42.
4. Sporanox(Itraconazole). JanssenPharmaceutica Products, L.P. FDA. Last accessed on May 2, 2007
