TITLE: Pilot Project D - Anticancer Effect of Novel Compounds Derived from Gorgonian Octocorals inthe Caribbean SeaJO-LEADERS: UPRCCC - Abimael Rodriguez, Ph.D., Professor, Department of ChemistryMDACC - Yasuko Kondo, M.D., Ph.D., Assistant Professor, Neurosurgery-ResearchABSTRACTIn a pre-pilot study funded by the present U54 grant, we found that eupalmerin acetate (EPA), which wasselected from 15 compounds derived from marine organisms in the Caribbean Sea, has significant anticancereffect on human malignant glioma cells both in vitro and in vivo. We have also demonstrated that EPA inducesapoptosis in malignant glioma cells via the c-Jun NH2-terminal kinase (JNK) pathway. As a successfulextension of our pre-pilot project, we have modified the structure of EPA and synthesized 10 additional EPAderivedcompounds to develop even more potent anticancer agents. We hypothesize that EPA or itsderivatives (collectively referred to as EPAs) will show anticancer effect in malignant qlioma and leukemia cellsboth in vitro and in vivo. Therefore, the objectives of this pilot project are 1) to determine the anticancer efficacyand mechanisms of EPAs in malignant glioma and leukemia cells in vitro, 2) to determine the anticancer effectof the lead compounds in the animal cancer xenograft model, and 3) to examine pharmacokinetics and toxicityof the lead compounds.Relevance of Pilot Project to the Overall PrioritiesThe goal of this proposal is to develop marine compounds isolated from the Caribbean Sea by an establishedscientist (UPR-Rio Piedras) into novel anticancer agents through collaboration of cancer specialists atMDACC. Our study is tightly associated with the U54 aims as the Co-leaders seek to continue building theirexisting partnership that started with a pre-pilot (pipeline) project.
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