Investigating Quinone-Mediated Treatments on the Warburg Effect

Miller, Jarred

Investigating Quinone-Mediated Treatments on the Warburg Effect

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MILLER_Investigating the Effects of Quinone-Mediated Treatments_HONORS_SPRING_2022_A.pdf (571.49 KB)

Date

2022-05

Authors

Miller, Jarred

Publisher

Honors Program, The University of Tampa

Abstract

Breast cancer is the most prevalent cancer amongst women in the United States, encompassing approximately 30% of all newly diagnosed cancers each year. It is also the second leading cause of cancer-related death in women in the United States. The main challenge in current therapeutic treatments is the increasing resistance of breast cancer cells to targeted therapies. Drug resistant cancer deaths are often the result of heterogeneous cell populations that may utilize different growth strategies. Drug resistant cancer cells prefer to generate ATP energy pools through the process of aerobic glycolysis (AG), known as the Warburg effect, rather than proceeding through oxidative phosphorylation (OXPHOS), to avoid a buildup of toxic reactive oxygen species (ROS). This proposal challenges the current paradigm that concurrent use of antioxidants with chemotherapy yields antiapoptotic effects through the investigation of capsaicin, resveratrol, and shikonin on two breast cancer cell lines, MCF-7 and MDA-MB-231. While MCF-7 cells are nondrug resistant and grow via glycolysis in combination with OXPHOS, MDA-MB-231 cells are drug resistant and utilize the Warburg effect as a growth strategy. We hypothesize that the quinones tested will drive an AG-OXPHOS switch in the MDA-MB-231 cell line by upregulation of OXPHOS genes w/ concomitant downregulation of AG genes, thereby increasing ROS and leading to apoptosis. The quinones’ ability to induce death in a breast cancer cell line was validated by administering three concentration levels of each quinone in short term culture. Concentration levels vary for each quinone depending on their prior efficacious measures from the researched studies. Cytotoxicity was assessed by CyQUANT NF Cell Proliferation Assay. Statistical significance in MDAMB- 231 cell viability as a response to capsaicin, resveratrol, and shikonin treatment was confirmed using ANOVAs (p-value = 0.0004, p-value = 0.0002, and p-value < 0.0001, respectively). This study is important, as it could elucidate quinones that may be useful as therapeutics against drug resistant cancer, as well as investigate mechanisms used by drug resistant cells committed to growth via Warburg.

Description

Recommended Citation: Miller, Jarred. “Investigating Quinone-Mediated Treatments on the Warburg Effect.” Honors Program, The University of Tampa, 2022. https://doi.org/10.48497/3F6Y-4K10.

Keywords

Warburg, Drug resistant, Breast cancer, Reactive oxygen species

Citation

Miller, Jarred. “Investigating Quinone-Mediated Treatments on the Warburg Effect.” Honors Program, The University of Tampa, 2022. https://doi.org/10.48497/3F6Y-4K10.