Electronic Theses and Dissertations

Date of Award

1-1-2019

Document Type

Thesis

Degree Name

M.S. in Pharmaceutical Science

First Advisor

Dale G. Nagle

Second Advisor

Marc Slattery

Third Advisor

Cole D Stevens

School

University of Mississippi

Relational Format

dissertation/thesis

Abstract

In spite of the current advances in both radiotherapy and surgical techniques as well as molecularly targeted therapies, over 90 percent of cancer mortality rate is due to metastases. Considering the pivotal role of metabolism in cellular physiology, there is no doubt that metabolic alterations are critical for metastatic progression. Cardiolipin (CL), the signature phospholipid of mitochondria, is linked to a variety of vital mitochondrial processes, like oxidative phosphorylation. Cardiolipin is a unique dimeric phospholipid which contains four fatty acyl chains. Moreover, the CL remodeling process is believed to be responsible for generation of immature CL species that contribute to tumor growth progression. Abnormalities in CL composition and/or content have been discovered in various solid tumors. Cancer cells prefer saturated fatty acids over polyunsaturated fatty acids to avoid apoptosis triggered by CL peroxidation in mitochondria. However, little is known about the biochemical basis of the action of CL remodeling on breast cancer cell proliferation and metastasis. The effects of two potent phospholipase inhibitors which are bromoenol lactone [BEL], a calcium-independent phospholipase A2 inhibitor, and halopemide, a phospholipase D inhibitor, were examined on MDA-MB-231, MCF-7 cell lines and their corresponding bone metastasis BoM and MCF-7/BoM cell lines to study the role of CL remodeling on the progression of breast cancer and CL extraction method from breast cancer metastatic cells were established.

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