1. THE IN VITRO EFFECTS OF BRYOSTATIN-1 IN CONJUNCTION WITH TEMOZOLOMIDE ON U87MG HUMAN GLIOBLASTOMA MULTIFORME CELLS Stefani Fults, BA & Jeffrey P. Thompson, Ph.D. York College of Pennsylvania Department of Biological Sciences INTRODUCTION Marine animals have led to some of our greatest medical advances. Bryostatin-1, a macrolactone isolated from the bryozoan Bugula neritina, has shown anti-cancer, anti-tumor, and immunostimulant activities in developing research. Although Bryostatin-1 has proven to be relatively ineffective on its own, combined with existing chemotherapeutic drugs, it can enhance the drugs’ effectiveness (Baryza et al 2004, Kijjoa and Sawangwong 2004). This study will attempt to use Bryostatin-1 as a successful cancer therapy by jointly administering the drug with a Temozolomide (a widely used chemotherapeutic drug) and applying them to a Glioblastoma multiforme model. No known research has been accomplished using bryostatins to increase cell death in U87MG human Glioblastoma multiforme cells. The goal of this study is to provide further information in the field of cancer research and hopefully provide the knowledge needed to develop a new treatment for Glioblastoma multiforme. METHODS U87MG HUMAN GLIOBLASTOMA MULTIFORM CELL LINE Cells grown to confluency Experiment 1 Compare the effects of Bryostatin-1 against GBM cells without the presence of Temozolomide Experiment 2 Compare the effects of Temozolomide against GBM cells without the presence of Bryostatin-1 Experiment 3 Compare the effects of Bryostatin-1 and Temozolomide against GBM cells. Plate and Treat Cells Bryostatin-1 concentrations: 0-110.5nM Cells allowed to incubate for 2 days Plate and Treat Cells Temozolomide concentrations: 0-110uM Cells allowed to incubate for 2 days Plate and Treat Cells Temozolomide and Bryostatin-1 concentrations Cells allowed to incubate for 2 days Determine Cell Viability Cell Titer 96 Assay Absorbency measured using Wallac 1420 Multilabel Counter ACKNOWLEDGEMENTS Dr. Jeffrey P. Thompson, Mentor Dr. Karl Kleiner Dr. Carolyn Mathur Dr. Wendy Boehmler RESULTS  Bryostatin-1 alone was found to significantly inhibit the growth of U87MG cells.  Temozolomide was found to inhibit the growth of U87MG cells.  Temozolomide combined with Bryostatin-1 was found to increase cell growth of U87MG cells. DISCUSSION  Bryostatin-1 and Temozolomide were effective at inhibiting U87MG cell growth in vitro individually.  Bryostatin-1 did not enhance the cytotoxicity of the chemotherapeutic drug Temozolomide when used against in vitro U87MG.  Bryostatin-1 disrupted Temozolomide’s cytotoxicity and allowed the U87MG cells to grow uninhibited. OBJECTIVES  Determine the dose-response relationship of Bryostatin-1 to U87MG human Glioblastoma multiforme cells  Determine the dose-response relationship of Temozolomide to U87MG human Glioblastoma multiforme cells  Determine the dose-response relationship of Bryostatin-1 combined with Temozolomide to U87MG human Glioblastoma multiforme cells LITERATURE CITED Baryza, J.L., Brenner, S.E., Craske, M.L., Meyer, T. and Wender, P.A. 2004. Simplified Analogs of Bryostatin with Anticancer Activity Display Greater Potency for Translocation of PKCd-GFP. Chemistry and Biology 11:1261-1267. Kijjoa, A. and Sawangwong, P. 2004. Drugs and Cosmetics From the Sea. Marine Drugs 2:73-82. http://research.calacademy.org/redirect?url=http://researcharchive.calacademy.org/research/izg/SFBay2K/bugula.htm Molecular structure of Bryostatin-1 http://www.mdpi.com/1660-3397/2/2/73/pdf Molecular structure of Temozolomide http://www.sigmaaldrich.com/catalog/ProductDetail.do?lang=en&N4=76899|F LUKA&N5=SEARCH_CONCAT_PNO|BRAND_KEY&F=SPEC http://www.serc.si.edu/labs/benthic_ecology/plotinfo.aspx