Priority Reports Trastuzumab-Resistant HER2-Driven Breast Cancer Cells Are Sensitive to Epigallocatechin-3 Gallate Sean F. Eddy1, Susan E. Kane2 and Gail E. Sonenshein1 1 Department of Biochemistry and Women's Health Interdisciplinary Research Center, Boston University School of Medicine, Boston, Massachusetts and 2 Division of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, California Requests for reprints: Gail E. Sonenshein, Department of Biochemistry, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118. Phone: 617-638-4120; Fax: 617-638-4252; E-mail: gsonensh@bu.edu. Overexpression of the epidermal growth factor receptor family member HER2 is found in 30% of breast cancers and is a target for immunotherapy. Trastuzumab, a humanized monoclonal antibody against HER2, is cytostatic when added alone and highly successful in clinical settings when used in combination with other chemotherapeutic agents. Unfortunately, HER2 tumors in patients develop resistance to trastuzumab or metastasize to the brain, which is inaccessible to antibody therapy. Previously, we showed that the green tea polyphenol epigallocatechin-3 gallate (EGCG) inhibits growth and transformed phenotype of Her-2/neu–driven mouse mammary tumor cells. The different modes of action of EGCG and trastuzumab led us to hypothesize that EGCG will inhibit HER2-driven breast cancer cells resistant to trastuzumab. We studied trastuzumab-resistant BT474 human breast cancer cells, isolated by chronic trastuzumab exposure, and JIMT-1 breast cancer cells, derived from a pleural effusion in a patient who displayed clinical resistance to trastuzumab therapy. EGCG treatment caused a dose-dependent decrease in growth and cellular ATP production, and apoptosis at high concentrations. Akt activity was suppressed by EGCG leading to the induction of FOXO3a and target cyclin-dependent kinase inhibitor p27Kip1 levels. Thus, EGCG in combination with trastuzumab may provide a novel strategy for treatment of HER2-overexpressing breast cancers, given that EGCG can cross the blood-brain barrier. Cancer Res 2007;67(19):9018–23 October 1, 2007. doi: 10.1158/0008-5472.CAN-07-1691 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.