Date of Award

2008

Degree Type

Dissertation

Department

Chemistry

First Advisor

Kalafatis, Michael

Subject Headings

Protein kinase CK2, Mouse leukemia complex -- Chemotherapy, Cancer -- Chemotherapy, Casein kinase 2, DMAT, MEG-0, Leukemia, Electronic books. local

Abstract

Cancer is so widespread and lethal that it can be considered the biggest health problem of our century. Cancer drug development is a real challenge. Efforts outlined in this work were directed towards showing solid evidence that casein kinase 2 inhibitors can be used as a starting point for the development of potential cancer therapy. We first studied the effect of a specific CK2 inhibitor, DMAT, in a malignant megakaryoblastic leukemia cell line (MEG-01). Treated cells grew at a significantly lower rate than non-treated cells. Apoptosis was induced by DMAT in MEG-01 cells, dose and time dependent. When stimulated with DMAT, MEG-01 cells produced platelets in vitro and in vivo. These platelets were found to have a normal phenotype and normal function. MEG-01 tumor bearing mice had tumor growth inhibition due to DMAT. These mice had MEG-01 cells spleen infiltration, splenomegaly and high platelets counts. An in vivo pilot toxicity study showed that DMAT is not toxic to mice. Breast cancer, colon cancer and melanoma cells were treated with DMAT. We observed that in vitro DMAT induces significant proliferation arrest and apoptosis at a similar level in all the cancer cell lines tested. All the tumor bearing mice treated with DMAT showed tumor growth inhibition but this was dependent oh hormone level for breast cancer and varied with the type of cancer analyzed

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