Abstract
Abstract A distinctive tumor microenvironment associated with chronic inflammation, cancer development, and drug resistance in triple-negative breast cancer (TNBC) affect disproportionally Caucasian and African American women. PURPOSE: This investigation presents possible new biomarkers that could be modulated by the natural compound pentagalloyl glucose (PGG) in MM-231 (Caucasians) and MM-468 (African American) TNBC cells. METHODS: Cytokine arrays, ELISA, RT-PCR, flow cytometry, and Western analysis were performed. RESULTS: PGG reduced the expression of GRO-α/CXCL1 pro-inflammatory cytokine, which is associated with tumor recurrence and chemoresistance. PGG inhibited IκBKE and MAPK1 gene and protein expression indicating a possible signaling pathway for CXCL1 downregulation through NFκB and MAPK signaling. PGG also inhibited cell growth in both cell lines, which could be associated with a decrease in CXCL1 levels. Besides, PGG induced apoptosis, modulating numerous genes, including caspases, TNF, and TNF superfamily receptor genes. Remarkably, PGG promoted a 154.6-fold increase in TNF expression in African American compared to 14.6-fold in Caucasian cells. CONCLUSION: the findings show PGG potential in ameliorating inflammatory processes and reducing resistance to chemotherapeutic agents since TNF has been demonstrated to sensitize tumor cells. Thus, the use of PGG may be a helpful tumor therapeutic strategy to increase tumor sensitivity to chemotherapy and slow cancer progression. Citation Format: Samia Messeha, Karam F.A. Soliman, Patricia Mendonca, Sumaiah Alghamdi. Pentagalloyl glucose inhibits GRO-α/CXCL1 pro-inflammatory cytokine and induces expression of apoptosis-related genes in racially different TNBC 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-116.
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