Date of Graduation

2017

Document Type

Thesis

Degree Type

MS

College

Eberly College of Arts and Sciences

Department

Chemistry

Committee Chair

Jonathan W Boyd

Committee Co-Chair

Suzanne Bell

Committee Member

Peng Li

Abstract

The phenomenon of hormesis, characterized by beneficial low-exposure stress-protective effects, has experienced increasing interest by the scientific community. Elucidating the underlying cellular signaling pathways that lead to a new homeostatic state can provide crucial information about new therapeutic targets to prevent and treat diseases. Commonly investigated for hormetic behavior are plant-based substances (phytochemicals), such as quercetin, epigallocatechin gallate, curcumin, and resveratrol. The polyphenol resveratrol, found in peanuts, grapes, and subsequently in wine, is known for a variety of effects---beneficial and detrimental---depending on the investigated cell type and concentration. In HepG2 cells, an increase in proliferation has been observed previously at doses between 10 microM to 100 microM after 16 hours, while higher doses decreased cell viability markedly, eventually leading to cell death. For other compounds, literature searches provide conflicting data on the hormetic capabilities and subsequently on the associated concentrations. This work aims to clarify the concentration and exposure duration dependence in hormesis. The four aforementioned compounds were screened for their hormetic behavior in a human liver cancer model by assessing the effects of varying concentrations on metabolic activity and plasma membrane integrity. Quercetin, epigallocatechin gallate, and curcumin did not show hormetic properties in the investigated concentration range during a 24-hour exposure. Resveratrol qualified for further experiments where cells were subjected to 0.1 to 500 microM for six, twelve, 24, 48, and 72 hours. A significant change in metabolic activity at concentrations of 50, 100, and 250 microM was found between twelve and 24 hours, as well as a significant increase in plasma membrane degradation after 24 hours at doses higher than 100 microM. This demonstrates a noticeable change in cellular behavior between the twelve- and 24-hour mark, associated with resveratrol concentrations from 50 to 250 microM. Future research should include real-time assessment of energy markers, preferably up to 24 hours, to pinpoint timepoints of metabolic switches, and subsequently study the changes that underlie hormesis at these timepoints.

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