Chemical Determinants of Pro-oxidant and Oral Cancer Inhibitory Activity of Dietary Polyphenols
Open Access
- Author:
- Capece, Gina
- Millennium Scholars Program:
- Biochemistry and Molecular Biology (B M B)
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisor:
- Joshua D Lambert, Thesis Supervisor
David Scott Gilmour, Honors Advisor - Keywords:
- oral cancer
cancer
polyphenol
cell culture
oxidative stress
ROS - Abstract:
- Oral cancer is a serious yet largely overlooked problem both nationally and globally. In the United States alone, a little over fifty thousand people are diagnosed with oral cancer each year, and approximately ten thousand people die from oral cancer per year. People with oral cancer experience many debilitating symptoms such as problems with speaking, swallowing, and eating. However, many of these severe symptoms do not appear until the disease has progressed to a much later stage, and the survival rate for oral cancer decreases significantly upon late detection. In order to discover and develop chemopreventive agents as well as therapeutics for such a severe disease, researchers have begun investigating natural compounds, such as dietary polyphenols, for potential use. Polyphenols are found in a wide variety of dietary sources, such as kale and other bitter greens, citrus fruits, red onions, red wine, tea, and coffee. These organic compounds have frequently been studied for their antioxidant, anti-inflammatory and anti-cancer properties. In normal healthy cells, polyphenols are recognized for their antioxidant behavior, but in cancerous cells, polyphenols are suspected to display prooxidant behavior as a way to inhibit cancer cell growth. This experiment focused on evaluating if prooxidant behavior was exhibited by polyphenols when the compounds were used to treat human oral cancer cells (SCC-25). My hypothesis predicted that dietary polyphenols relied on the induction of mitochondrial oxidative stress as the critical mechanism for their oral cancer inhibitory activity. First, I examined general cytotoxicity of apigenin, chrysin, eriodictyol, fisetin, naringenin, and quercetin. Then I assessed polyphenol cytotoxicity with an antioxidant present, and I measured intracellular reactive oxygen species (ROS) production after polyphenol treatment. All polyphenols examined in my experiments had a dose-dependent cytotoxicity in SCC-25 cells. Cell viability was restored in most SCC-25 cells after co-treatment with a general antioxidant, but co-treatment with fisetin or eriodictyol and the antioxidant did not attenuate cytotoxicity. SCC-25 cells treated with quercetin displayed a significant increase in ROS production after 24 hours, but some SCC-25 cells had only a slight increase or no difference in ROS production after treatment with other polyphenols. There was no clear correlation between ROS production and cytotoxicity, as quercetin was the least cytotoxic, but SCC-25 cells treated with quercetin produced the most ROS after 24 hours. If further studies confirm these findings, polyphenols that are cytotoxic in oral cancer cells could be used to develop novel oral care treatments.