Title

Anti-Cancer Effect of Fluorinated Caffeic Acid Phenethyl Ester in Human Multiple Myeloma Cells

Date of Award

2017

Degree Type

Thesis

Degree Name

Master of Science (MS)

First Advisor

Xinyu Wang, PhD

Second Advisor

Rangiah Shashidharamurthy, PhD

Third Advisor

Abigail Hielscher, PhD

Fourth Advisor

Richard E. White, PhD, FAHA

Abstract

Multiple myeloma (MM) is a plasma cell malignancy that occurs in the bone marrow. It is responsible for approximately 1% of all cancer related deaths and remains as an incurable disease. Recently, polyphenolic compounds have demonstrated therapeutic potential in treating various cancers, including hematological cancers. Preliminary data has shown that caffeic acid phenethyl ester (CAPE), a polyphenolic compound found in bee hive propolis, can inhibit MM cell growth and cause cell death through apoptosis. Fluorinated caffeic acid phenethyl ester (FCAPE), a novel derivative of CAPE that was previously synthesized in our lab, could potentially serve as an effective multiple myeloma treatment. Because FCAPE was found to be more stable than CAPE in rat plasma, it could be a better candidate for multiple myeloma treatment than its parental compound. We hypothesize that FCAPE inhibits growth of and induces apoptosis in MM cells. To test our hypothesis, we first evaluated the effect of FCAPE on the growth of MM cell lines, RPMI 8226, NCI-H929 and U266. We then examined FCAPE induction of apoptosis in MM cells, through flow cytometric analysis. In addition, western blot imaging of various pro and anti-apoptotic proteins such as PARP, MCL-1, Bcl-xl and various caspase enzymes, was used to further confirm the role of apoptosis in MM cell death. To further explore the potential mechanism of FCAPE’s toxicity, cell viability was measured after pretreatment with a known antioxidant, Nacetyl cysteine (NAC) and FCAPE treatment. In addition, cell viability was measured after pretreatment, with buthionine sulfoxide (BSO), a known inhibitor of glutathione, and FCAPE treatment. These experiments provide some insight into the mechanism of FCAPE toxicity in myeloma cell lines.

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