Date of Award
Master of Science (MS) in Biology
Dr. Lori Hensley
Ewing sarcoma (ES) is an aggressive pediatric bone cancer with low five-year survival rates, particularly with recurrent disease because ES often becomes resistant to chemotherapy in these recurrences. Cannabidiol (CBD) has been identified as a potentially promising therapeutic for patients with ES. In other cancer types, CBD has demonstrated effects on two major proteins that contribute to chemotherapy resistance. The first, Poly (ADP-ribose) Polymerase I (PARP1), is a DNA damage repair enzyme that is overexpressed in recurrent ES. Though chemotherapy induces DNA damage in these cancer cells, the high levels of PARP1 facilitate repair of the DNA, allowing the mutated DNA to be duplicated and subsequent proliferation of the cancer to occur. CBD has been shown to cleave PARP1 in colon, prostate, and breast cancer cell lines. The second, survivin, is a protein that inhibits apoptosis, is overexpressed in ES, and its reduction leads to decreased growth in ES cell lines. The hypothesis of this study was that CBD would both cleave PARP1 and downregulate survivin expression in the A673 ES cell line. Enzyme-linked immunosorbent assay (ELISA) data demonstrated cleavage of PARP1 by CBD at concentrations of 30mM and higher. However, survivin expression was increased at the same concentrations. These data suggest further investigation into the use of CBD to modulate pathways known to contribute to chemotherapy resistance is warranted in an effort to improve the prognosis for patients with recurrent ES.
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