CombinedNSP
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 Posted: Dec Thu 14, 2006 5:11 pm Post subject: Soy - Breast Cancer - Scientific Abstract |
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Soy - Breast Cancer - Scientific Abstract
Some one asked me for this and thought the group might like to see it, also... Cytotoxic Activity of Epidermal Growth Factor-Genistein against Breast Cancer Cells1 Fatih M. Uckun,2 Rama Krishna Narla, Xiao Jun, Tamer Zeren, Taracad Venkatachalam,Kevin G. Waddick, Alexander Rostostev, and Dorothea E. Myers Departments of Oncology [F. M. U., R. K. N.], Chemistry [T. V.], Biochemistry [A. R.], Immunobiology [X. J.],and Biotherapy [D. E. M., X. J., K. G. W.] and Drug Discovery Program [F. M. U., R. K. N., T. V., A. R., D. E. M.],Wayne Hughes Institute, St. Paul, Minnesota 55103, and Department of Therapeutic Radiology, University of Minnesota, Minneapolis, Minnesota 55455 [T. Z., K. G. W.]
Abstract
The receptor (R) for epidermal growth factor (EGF) is expressed at high levels on human breast cancer cells and associates with ErbB2, ErbB3, and Src proto-oncogene family protein tyrosine kinases (PTKs) to form membrane-associated PTK complexes with pivotal signaling functions. Recombinant human EGF was conjugated to the soybean-derived PTK inhibitor genistein (Gen) to construct an EGF-R-directed cytotoxic agent with PTK inhibitory activity. The EGF-Gen conjugate was capable of binding to and entering EGF-R-positive MDA-MB-231 and BT-20 breast cancer cells (but not EGF-R-negative NALM-6 or HL-60 leukemia cells) via its EGF moiety, and it effectively competed with unconjugated EGF for target EGF-R molecules in ligand binding assays.
EGF-Gen inhibited the EGF-R tyrosine kinase in breast cancer cells at nanomolar concentrations,whereas the IC50 for unconjugated Gen was 10 µM. Notably, EGF-Gen triggered a rapid apoptotic cell death in MDA-MB-231 as well as BT-20 breast cancer cells at nanomolar
concentrations. The EGF-Gen-induced apoptosis was EGF-R-specific because cells treated with the control granulocyte-colony stimulating factor-Gen conjugate did not become apoptotic.
Apoptosis was dependent both on the PTK inhibitory function of Gen and the targeting function of EGF, because cells treated with unconjugated Gen plus unconjugated EGF did not undergo apoptosis. The IC50s of EGF-Gen versus unconjugated Gen against MDA-MB-231 and BT-20 cells in clonogenic assays were 30 ± 3 nM versus 120 ± 18 µM (P < 0.001) and 30 ± 10 nM versus 112 ± 17 µM (P < 0.001), respectively. Thus, the EGF-Gen conjugate is a >100-fold more potent inhibitor of EGF-R tyrosine kinase activity in intact breast cancer cells than unconjugated Gen and a >100-fold more potent cytotoxic agent against EGF-R+ human breast cancer cells than unconjugated Gen. Taken together, these results indicate that the EGF-R-associated PTK
complexes have vital antiapoptotic functions in human breast cancer cells and may therefore be used as therapeutic targets.
Soybean-derived Drug to Be Tested on Breast Cancer Patients
A soybean-derived molecule that acts like a smart bomb by seeking out cancer cells and interfering with their ability to survive and multiply is set to be tested on late-stage breast cancer patients, according to an article in the Twin Cities Star-Tribune. Researcher Dr.Fatih Uckun, said the molecule has caused human breast tumors transplanted into mice to shrivel up and die. The molecule blocks the action of an enzyme that tumor cells need to survive and multiply, Uckun said. His findings appear in the April issue of the Journal Clinical Cancer Research. -Sammye Lamb |
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