Professor of Chemistry
Ph.D. Kyoto University, 1985
(Bioorganic, Organic, and Biostructural Chemistry)
The Sasaki group is developing novel medical and food/supplement technologies based on artemisinin, a natural product isolated from Artemisia annua L. Artemisinin is a part of the current standard treatment for malaria infection in humans. Artemisinin contains an endoperoxide group that reacts with intracellular iron to generate toxic radical species. Cancer cells undergoing rapid proliferation intake large quantities of the essential nutrient iron through up-regulation of transferrin receptor. Artemisinin has demonstrated highly selective cytotoxicity towards cancer cells in vitro and in vivo. We have found that the anti-cancer activity of artemisinin can be greatly enhanced by delivering the compound directly to the cellular iron uptake machinery. Also, dimers of artemisinin have shown highly potent anticancer activities that are equivalent to that of Taxol in cell-based assays. Recently, we discovered that artemisinin derivatives induce a specific down-regulation of survivin, an anti-apoptotic protein critical to cancer cell survival.
The natural product artemisinin is currently available as a supplement in the U.S. We hypothesize that artemisinin provides an effective and economical treatment for cancer in dogs and other pets. We collaborate with a group in Washington State University to perform clinical trials of artemisinin in dogs with non-Hodgkins lymphoma (NHL). This disease in dogs is an excellent, naturally occurring model of the human disease. Survivin, which we hypothesize will decrease in response to artemisinin in vivo, is over-expressed in canine NHL. Lymphoma is one of the most common forms of cancer in dogs.
Artemisinin is also effective against parasite infection in animals. For example, avian coccidiosis is considered to be one of the most economically devastating parasitic diseases in the poultry industry. Chicken feed mixed with Artemisia leaves that contain high artemisinin show an increased average body weight and egg production. New animal feeds with Artemisia leaves could make organic meat products available to consumers at a significantly lower cost. We are collaborating with groups in Washington State University and USDA-ARS/Appalachian Farming Systems Research Center to optimize the growth conditions of a high artemisinin producing cultivar in Eastern Washington, and to investigate the biological effects of Artemisia extracts.
Lai, H., Nakase, I., Lacoste, E., Singh, N. P., Sasaki, T. Artemisinin-transferrin Conjugate Retards Growth of Breast Tumors in the Rat. Anticancer Res. in press (2009).
Nakase, I., Gallis, B., Takatani-Nakase, T., Oh, S., Lacoste E., Singh, N.P., Goodlet, D.R.,
Tanaka, S., Futaki, S., Lai, H. and Sasaki, T. Transferrin receptor-dependent cytotoxicity of
artemisinin-transferrin conjugates on prostate cancer cells and induction of apoptosis. Cancer
Letters 274, 290-298 (2009)
Oh, S., Kim, B.J., Singh N. P., Lai, H. & Sasaki, T. Synthesis and Anti-cancer Activity of Covalent
Conjugates of Artemisinin and a Transferrin-receptor Targeting Peptide. Cancer Lett. 272, 110- 121 (2008)
Nakase, I., Lai, H., Singh, N. P. & Sasaki, T. Anticancer Properties of Artemisinin Derivatives and Their Targeted Delivery by Transferrin Conjugation. Int. J. Pharm. 354, 28-33 (2007)
Jones, J. W., Sasaki, T., Goodlett, D. R. & Turecek, F. Electron Capture in Spin-Trap Capped Peptides. An Experimental Example of Ergodic Dissociation in Peptide Cation-Radicals. J. Am. Mass-spect. Soc. 18, 432-444 (2007).
Kim, B. J. & Sasaki, T. Recent Progress in the Synthesis of Artemisinin and its Derivatives.
Organic Preparations and Procedures 38, 1 – 80 (2006).
Lai, H., Sasaki, T., Singh Narendra, P. & Messay, A. Effects of artemisinin-tagged holotransferrin on cancer cells. Life sciences 76, 1267-79 (2005).
Lai, H., Sasaki, T. & Singh Narendra, P. Targeted treatment of cancer with artemisinin and artemisinin-tagged iron-carrying compounds. Expert opinion on therapeutic targets 9, 995-1007 (2005).
Kim, B. J. & Sasaki, T. Synthesis of O-Aminodihydroartemisinin via TMS Triflate Catalyzed C-O Coupling Reaction. Journal of Organic Chemistry 69, 3242-3244 (2004).