Planta Med 2012; 78 - PI289
DOI: 10.1055/s-0032-1320976

Synthesis of ellagic acid peracetate and antitumor efficacy with enhancement of immunity

Y Ren 1, M Wei 2, PC Still 1, X Chen 3, 4, 5, K Himmeldirk 3, AD Kinghorn 1, 6, J Yu 6, 7
  • 1Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy
  • 2Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio 43210
  • 3Department of Chemistry and Biochemistry
  • 4Edison Biotechnology Institute,
  • 5Department of Biomedical Sciences, Molecular and Cellular Biology Program, Ohio University, Athens, Ohio 45701
  • 6Comprehensive Cancer Center
  • 7Division of Hematology/Oncology, College of Medicine and School of Public Health, The Ohio State University, Columbus, Ohio 43210

A synthetic method was developed for the total synthesis of ellagic acid (EA) and ellagic acid peracetate (EAPA). A subcutaneous B16 melanoma tumor model of C57BL/6 immunocompetent mice was used to evaluate the antitumor efficacy of the two chemicals. After the treatment of EA and EAPA for three weeks, using a dose of 0.5mg/kg per mouse, tumors were removed, weighed, photographed, and the average tumor size was calculated and compared. The expression of CD107a and the production of IFN-γ in natural killer cells and the levels of white blood cells and other immune cells were determined, with the weights of bodies, livers, and spleens of normal mice also being evaluated. The results showed that administration of EAPA significantly suppressed B16 melanoma growth in mice without affecting natural killer cell activity and was more effective than EA. EAPA increased white blood cell quantity in several organs or tissues including peripheral blood, bone marrow, and liver, and such effects were greater than those of EA. Furthermore, neither compound showed toxicity to mice. This study suggests that EAPA may be investigated further as a new immunity-stimulatory anticancer drug candidate with potential low toxicity for cancer treatment (Partial support is from grant P01 CA125066 from the National Cancer Institute, NIH, Bethesda, MD, MetaCor Pharmaceuticals Inc., and the Edison Program of the State of Ohio).