Abstract 1592: The role of beta-adrenergic receptor agonists and inhibitors on the efficacy of Doxorubicin in TNBC cell lines
Authors: Burwell Alanna , Andrews Portia , Lopez Dayami , Kimbro K. Sean 
Published: April 2023

Despite the significant advancements in breast cancer (BCa) research and potential therapeutic targets, mortality rates for African American (AA) women remain high compared to other ethnic groups. In the United States, BCa is the second leading cause of cancer-related deaths and is commonly classified by the expression of molecular markers. Treatment and prognosis are determined by the presence and absence of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), and, more recently, the androgen receptor (AR). AA women are more likely to be diagnosed with triple-negative breast cancer (TNBC) and experience a higher risk of BCa mortality than European American women (EA), creating a survival disparity. Biological and non-biological factors are implicated in the difference between EA and AA women contributing to the racial disparities in BCa mortality. Potential implications of this disparity in AA women have been linked to treatment, health care access, socioeconomic status (SES), stress, genetics, and comorbidities. Due to the fraction of available chemotherapeutics for TNBC and the survival disparity in AA women, identifying mechanisms contributing to this aggressive, hard-to-treat BCa is warranted. Studies examining psychological stress and its connection has been shown to contribute to the etiology and aggressiveness of BCa. A direct link has been made in animal models between induced psychological stress and tumor development.Specifically, psychological stress has resulted in higher catecholamine levels and is associated with cancer, resulting in higher incidence, aggression, and mortality. Norepinephrine and epinephrine signal through β-Adrenergic receptors (β-ARs), and these interactions have been shown to decrease apoptosis in prostate cancer cells, increasing malignancy in BCa through the p38 MAPK signaling pathway, and promote BCa stem-like cells. Inhibitors of β-ARs or beta-blockers have been shown to improve the efficacy of chemotherapeutics and decrease the risk of heart failure in cancer patients receiving anthracycline therapy. In this study, we use four TNBC cells (MDA-MB-231, HCC-1143, MDA-MB-468, HCC-1806) that differ in the percentage of West African Ancestry (WAA); we identify differential expression of the ADRB2 protein across all cell lines utilizing flow cytometry. We also show that the non-selective inhibitor of ADRB1 and ADRB2, propranolol, increases the efficacy of Doxorubicin in some cells, which is determined by IC50. We find that the agonist norepinephrine (NE) has no significant impact on cellular growth but impacts the cell's response to Doxorubicin. Here we show that beta-blockers may provide a clinical benefit in combination with Doxorubicin which is dependent upon cell line, and that the β-AR is a promising target for treating TNBC.

Citation Format: Alanna Burwell, Portia Andrews, Dayami Lopez, K. Sean Kimbro. The role of beta-adrenergic receptor agonists and inhibitors on the efficacy of Doxorubicin in TNBC cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1592.