Abstract 2972: Urolithin A decreases cell proliferation of three genetically diverse glioblastoma multiforme cell lines

Abstract

Abstract Glioblastoma multiforme is one of the most common and malignant tumors of the central nervous system, remaining incurable with a median survival time of only 15 months. Over the past 50 years there has been little change in this overall survival rate, due to the many challenges in treating glioblastoma, including molecular complexity, tumor location, and resistance towards standard therapies. Therefore, an improved method for treating glioblastoma is urgently needed. Urolithin A is a natural biometabolite from ellagitannins and ellagic acid, which can be found in pomegranates, berries, and nuts. Urolithin A exhibits anti-cancer activities in several cancer cell lines, including prostate, colon, and bladder cancer cells. However, the anti-cancer activities of urolithin A have yet to be characterized in glioblastoma multiforme. In this project, we investigated whether urolithin A could reduce human glioblastoma cell proliferation by conducting clonogenic assays and cell cycle analysis in three genetically diverse human glioblastoma cell lines: U87MG, T98G, and LN229. Clonogenic assay results showed that urolithin A significantly decreased cell proliferation in a dose-dependent manner in all three glioblastoma cell lines. Depending on the different cell lines, the cell proliferation was inhibited at concentrations of 10 to 60 µM urolithin A. In addition, cell cycle analysis via flow cytometry found that urolithin A was capable of arresting cell cycle progression in either the G2/M or S phase of the cell cycle in U87 and LN229 or T98G cells, respectively. In conclusion, we have found that urolithin A can reduce cell proliferation and alter cell cycle progression of three genetically diverse glioblastoma cell lines. Importantly, urolithin A can pass the blood-brain barrier and has previously shown to be non-toxic in humans, a prerequisite for a drug to treat glioblastoma. Therefore, urolithin A has the potential to be used as a novel drug which can be combined with current standard methods to improve the efficacy of glioblastoma treatment. In the future, we plan to investigate specific signaling pathways involved in apoptosis, cellular proliferation, and cell cycle arrest. Once we elucidate the specific mechanisms we will investigate the efficacy of urolithin A in vivo, using an animal model. If successful, urolithin A will have the potential to be used alongside radiation and chemotherapy to further reduce glioblastoma cell proliferation. Citation Format: Alexandra Lynn Hearne, Dakota Brockway, Shiyong Wu, Yunsheng Li. Urolithin A decreases cell proliferation of three genetically diverse glioblastoma multiforme cell lines [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2972.