Antiproliferative Effect of Ascorbate on Breast Epithelial Cells Acts via a Pro-Oxidant Mechanism of Hydrogen Peroxide Production
Open Access
- Author:
- Martin, Robert Joseph
- Area of Honors:
- Letters, Arts, and Sciences (Abington)
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Dr. Eric Paul Ingersoll, Thesis Supervisor
Dr. David E Ruth, Thesis Honors Advisor
Dr. Thomas McGuire, Faculty Reader - Keywords:
- ascorbate
vitamin c
hydrogen peroxide
glutathione
MCF-10F
E2
C5
T4
breast epithelial cell lines
catalase
adjuvant
antiproliferative
pro-oxidant
in vitro
GLUT1
GLUT3
dehydroascorbate
oxidative
oxidative stress
oxidative phosphorylation
glycolysis
5-mM
10-mM
milimolar concentrations
reactive oxygen species
super oxides
free radicals
redox
redox reactions
GAPDH - Abstract:
- Ascorbate, otherwise known as vitamin C, has been well known for its use in supplementation against the common cold, stimulating the immune system, but work originating with Linus Pauling suggests it may have anti-cancer properties. Ascorbate has a variety of proposed mechanism including: boosting immunological activity, cancer protein degradation, glycolytic enzyme inhibition, and reactive oxygen species scavenger depletion. One of the main supported mechanisms is that of hydrogen peroxide production to perturb redox homeostasis within cancer cells that cannot cope to the imposed redox stress. Cancer cells often lack enzymatic activity to control free radicals and hydrogen peroxide. In vitro culturing involved a variety of breast epithelial cell lines cultured in high-calcium medium and incubated for three days. Results suggest that ascorbate decreases cellular proliferation in a dose-dependent manner. The tumorigenic T4 cells warrant the use of a higher concentration of ascorbate possibly up to 30-mM, which has been found to be achievable in vivo. Catalase experimentation was used to target hydrogen peroxide; cell lines treated with both, ascorbate and catalase, exhibited a normalized growth resembling the control 0-mM flasks. Our negative results suggest ascorbate acts via a pro-oxidant mechanism to decrease cellular proliferation. High-dose ascorbate treatment as an adjuvant to cancer treatment offers a great method to further decrease cancer proliferation as shown in these in vitro studies.