Abstract P3-11-26: Investigating the synergistic anti-cancer effects on mitochondrial function in breast cancer cells using arctigenin, cinnamaldehyde, and chlorogenic acid individually and in combination

Abstract

Abstract One of the major obstacles in current breast cancer treatment efficacy is the ability of breast cancer cells to develop resistance to chemotherapeutic drugs. In addition, a second major obstacle is the off-target cytotoxicity of these drugs on normal cells, leading to debilitating side effects. Many of these current chemotherapeutics target DNA (repair, replication, division). As a result, the bystander effect to normal cells and tissues is significant. However, one major difference between cancer and normal cells is their metabolism. The Warburg Effect suggests that cancer cells prefer a glycolytic, hypoxic environment. Emerging studies have begun to delineate differences in mitochondrial function between cancer and normal cells. In this study, we sought to exploit this metabolic difference by investigating alternative breast cancer treatment options based on application of natural product components. Previous studies from our lab demonstrated the efficacy of a mixture of plant extracts in killing cancer cells. Proteomics studies showed significant mitochondrial disruption in the cancer cells compared to normal cells. Here, we investigate three of the main components, identified by Mass Spectometry, to determine their anticancer properties compared to the whole extracts’ mixture. Arctigenin, chlorogenic acid, and cinnamaldehyde all demonstrate anti-cancer activity. We hypothesize that each component of the whole extract causes breast cancer cell death by disruption of mitochondrial activity and metabolic shifts, and lead to an increase in oxidative stress that is further amplified by combination treatment. These small molecules were administered to MDA-MB-231 and MCF-7 breast cancer or normal MCF-10A and MCF-12F breast cells, either alone or in combination. To evaluate differences in cell response, mitochondrial integrity and metabolic shifts were evaluated by flow cytometry, fluorescence microscopy and the Agilent Seahorse XF Cell Mito Stress Test. The ladder measures the mitochondria’s oxygen consumption rate, basal respiration, ATP production, proton leak, maximal respiration, spare respiratory capacity, and non-mitochondrial respiration. This study provides evidence that targeting the mitochondria may be a more effective anticancer treatment and that either components of natural products or combinations thereof offer new approaches in treating breast cancer that significantly reduce off-target effects to normal cells. Citation Format: Caroline Schuster, Lauren S Gollahon. Investigating the synergistic anti-cancer effects on mitochondrial function in breast cancer cells using arctigenin, cinnamaldehyde, and chlorogenic acid individually and in combination [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-26.