Novel Drugs that Target ErbB2
Final rept. 1 May 2010-30 Apr 2012
TEXAS A AND M UNIV COLLEGE STATION
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Betulinic acid BA is relatively non-toxic in rodent studies and highly effective against melanoma in both in vivo and in vitro assays. Subsequent research in several laboratories indicates that BA inhibits growth of multiple tumor types including breast cancer. Studies in this laboratory show that BA inhibits prostate cancer cell and tumor growth in a xenograft model, and one of the underlying mechanisms of action is due to BA-induced proteasome-dependent degradation of specificity protein Sp transcription factors Sp1, Sp3 and Sp4. These proteins are highly expressed in several different cancer cell lines and tumors, whereas Sp1 levels in non-tumor tissue of rodents and humans is relatively low and decreases with age. In this study, we used BA as a model to investigate the effect of Sp1, Sp3 and Sp4 downregulation on BT474 and MDA-MD-453 breast cancer cells that express the oncogene EGFR2 ErbB2, HER2. The proposed research focused on the role of BA-induced Sp downregulation on cell and tumor growth, ErbB2 expression and the overall mechanisms associated with the anticancer activity of BA. We also investigated the role of BA in triple-negative MDA-MB-231 cells which do not express ErbB2.
- Anatomy and Physiology
- Medicine and Medical Research