Abstract 504: Anticancer effects of kaempferol through cell cycle arrest and the inhibition of proliferation in genetically distinct triple-negative breast cancer cells

Abstract Triple-negative breast cancer (TNBC) is one of the most known aggressive subtypes of breast cancer, affecting 1 in 3 newly diagnosed cancers in women. TNBC affects African-American women disproportionally in comparison to Caucasian women. Due to the lack of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptors (HER-2), it poses direct challenges to the efficacy of standard hormonal therapies. The current TNBC treatments present higher toxicity and multiple side effects. An alternative would be using natural compounds that have emerged as potential anticancer agents. Kaempferol is a major flavonoid aglycone found in many fruits, vegetables, and herbs, including grapes, tomatoes, broccoli, tea, and ginkgo biloba leaves. In this study, we investigated the differential effect of kaempferol on cell toxicity, cell growth, and underlying mechanisms in inducing cell cycle arrest in genetically different TNBC cells from Caucasian (MDA-MB-231) and African American (MDA-MB- 468) women. Kaempferol significantly inhibited cell growth in both the cell lines with a more profound effect against MDA-MB-231 (IC50: 43. 86 µM) compared to MDA-MB-468 cells (IC50: 53. 47 µM). Also, kaempferol treatment induced cell cycle arrest at S-phase in both cancer cell subtypes. The MDA-MB-231 cells showed a kaempferol effect at lower concentrations (6. 25µM and 12. 5µM), while MDA-MB-468 cells showed the same effect at higher concentrations (25µM and 50µM). Kaempferol also modulated CDK gene expression associated with cell cycle progression in breast cancer cells. The inhibition at S-phase is important in cancer treatment because it targets the highly proliferative nature of cancer cells characterized by uncontrolled cell division. This study indicates that, by inducing cell cycle arrest at the S-phase, kaempferol may interfere with cancer cell growth and proliferation by inhibiting DNA replication, offering potential therapeutic benefits. This approach could reduce side effects and increase treatment efficacy, providing hope for more effective interventions in the fight against TNBC. Citation Format: Sukhmandeep Kaur, Patricia Mendonca, Karam F. A. Soliman. Anticancer effects of kaempferol through cell cycle arrest and the inhibition of proliferation in genetically distinct triple-negative breast cancer cells abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 504.