Abstract A41: Dasatinib regulation of N-glycans induce anticancer activity in hematological and solid tumor malignancies.

Abstract

Abstract Glycans are carbohydrates covalently bound to proteins or lipids. Changes in their content and structure, particularly in asparagine-linked oligosaccharides, contribute to a variety of events during malignant transformation. These include the loss of cell-matrix adhesion, migration, invasion, metastasis, and evasion of cell death. High mannose glycans are not commonly present on the surfaces of normal mammalian cells or in serum, yet they play important roles in cancer cell biology. Therefore, modulation of glycan expression with drugs offers a promising therapeutic approach for various hematological and solid tumor cancers, several of which disproportionally afflict minority populations. Dasatinib, a dual inhibitor of Src and Abl tyrosine kinase, is used to investigate in vitro anti-cancer activity in several cancer cell lines: Jurkat lymphoblastic leukemia, Raji lymphoblastic lymphoma, SiHa cervical cancer, H1650 non small cell lung cancer, PC3N prostate cancer, SKOV3 ovarian cancer, and MCF7 breast cancer. To address how the carbohydrate moieties of the cancer cells are affected during treatment, the glycan profiles from treated cells are compared to non-treated cells and normal controls and analyzed by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). PCR arrays are used to profile glycosylation enzyme gene expression changes due to dasatinib-induced cytotoxicity. Protein expression arrays are used to investigate Src and Abl receptor tyrosine kinase signaling cascades. The results presented here demonstrate new evidence of glycosylation expression changes and the related mechanisms of their anticancer activity. Regulation of glycosylation is a promising therapeutic strategy for inducing anticancer activity through cell arrest, apoptosis, and autophagy. Citation Format: Mary R. Saunders, L. Renee Ruhaak, Cynthia Williams, David J. Olivos, Carol Stroble, Hyun Joo An, Suzanne Miyamoto, Carlito B. Lebrilla, Kit S. Lam. Dasatinib regulation of N-glycans induce anticancer activity in hematological and solid tumor malignancies. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A41.