Date of Degree

2-2018

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biology

Advisor(s)

Edward Kennelly

Committee Members

Jimmie Fata

Moira Sauane

Kurt Reynertson

Prabodhika Mallikaratchy

Subject Categories

Alternative and Complementary Medicine | Biology | Cancer Biology | Plant Sciences

Keywords

Garcinia, Breast cancer, Triple negative breast cancer, Proliferation

Abstract

Breast cancer continues to be the second leading cause of death in women, even with the recent advances in research that has led to an improved understanding of molecular pathways and targets. Increasing mortality due to recurrence and lack of targeted drugs, especially in aggressive breast cancer subtypes such as triple negative breast cancer, has gained attention from the research community. With nearly 50% of the commonly used cancer drugs being sourced from plants, bioactive small molecules derived from a natural origin have immense potential as therapeutics. This study focuses on the anti-proliferative activities of benzophenones isolated from the edible fruits of Garcinia xanthochymus and Garcinia paucinervis in breast cancer cells, particularly triple negative breast cancer cells. Novel benzophenones paucinones E – I from Garcinia paucinervis were tested on a panel of breast cancer cell lines MDA-MB-231, MCF-7 and SKBR-3 with varying receptor statuses. Paucinone H was active across the panel of cell lines studied, with IC50 values ranging from 10 to 20 µM. Since the activity was significant on MDA-MB-231, the possible pathways in MDA-MB-231 that paucinone H could modulate were investigated. Paucinone H induced apoptosis in a dose dependent fashion at IC50 concentration and decreased mitosis and migration of cells at half IC50 concentration in MDA-MB-231.

In addition to the research described above, a comprehensive review of dietary phytoestrogens and their impact on breast pathophysiology is also presented in Chapter 2. Appendices A and B discuss the use of UPLC-QTOF-MS based metabolomics to verify bio-activities of various vegetative organs of Garcinia oblongifolia and the identification of novel benzophenones from Garcinia paucinervis

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