Abstract PO-132: Rosmarinic acid-induced apoptosis and cell cycle arrest in triple-negative breast cancer cells

Abstract

Abstract Rosmarinic acid (RA) is a polyphenolic compound with various pharmacological properties, including anti-inflammatory, immunomodulatory, anti-mutagenic, antioxidant, and anticancer activities. This study evaluated the effects of RA in two racially different triple-negative breast cancer (TNBC) cell lines. One cell line was derived from Caucasian origin (MDA-MB-231), and another one was derived from an African American origin (MDA-MB-468). The apoptotic effect of RA was performed using An Annexin V-FITC Apoptosis Detection Kit, while the Propidium Iodide Flow Cytometry Kit was used to detect the cell cycle distribution. Gene expression profiling was established using Human Apoptosis PCR array. The results obtained show that RA significantly caused cytotoxic and antiproliferative effects in both cell lines in a dose- and time-dependent manner. It was noted that RA induced cell cycle arrest-related apoptosis and altered the expression of many apoptosis-involved genes differently. In MDA-MB-231 cells, RA arrested the cells in the G0/G1 phase. In contrast, RA causes S-phase arrest in MDA-MB-468 cells, leading to a 2-fold increase in the apoptotic effect compared to MDA-MB-231 cells. Furthermore, in MDA-MB- 231 cells, RA significantly upregulated the mRNA expression of three genes: Harakiri (HRK), tumor necrosis factor receptor superfamily 25 (TNFRSF25), and BCL-2 interacting protein 3 (BNIP3). In contrast, in the MDA-MB-468 cell line, RA induced a significant transcription activation in three genes, including TNF, growth arrest, and DNA damage-inducible 45 alpha (GADD45A), and BNIP3. Furthermore, RA repressed the expression of TNF receptor superfamily 11B (TNFRSF11B) in MDA-MB-231 cells in comparison to the ligand TNF superfamily member 10 (TNFSF10) and baculoviral IAP repeat-containing 5 (BIRC5) in MDA-MB-468 cells. In conclusion, the data suggest that the polyphenol RA may have a potential role in TNBC therapies, particularly in African American cells. Citation Format: Karam F.A. Soliman, Samia S. Messeha, Najla O. Zarmouh, Abrar Asiri. Rosmarinic acid-induced apoptosis and cell cycle arrest in triple-negative breast cancer cells [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-132.