Abstract
Abstract Glioblastoma is a highly aggressive astrocytoma known to form the most lethal type of primary brain tumor. Therapeutic options are limited because 94% of diagnosed patients survive less than five years. Glioblastoma malignancy is attributed to uncontrolled cellular proliferation, increased angiogenesis, apoptosis resistance, and local invasion. The Homologous small GTPases of the Rho family, Rac1 and Cdc42, are critical regulators of the invasion and migration of glioblastoma cells. Previous studies have found a correlation between the high expression of Rac and CDC42 and the highly invasive characteristics of GBM in vivo. Our group characterized the small molecule compound MBQ-167 as a potent dual inhibitor of Rac and Cdc42 in breast and pancreatic cancer and have shown its utility in cell and mouse models of metastasis. In this project, we tested the hypothesis MBQ-167 is also a valid therapy option for glioblastoma. The T98G glioblastoma cell line was treated with varying concentrations (62 nM to 1000 nM) of MBQ-167 for 24 hrs, and effects on Rac/PAK activation (at 24 hours) was determined through active GTP bound Rac pulldowns, cell viability (at 48 and 96 hours) through MTT assays, and cellular migration (at 12, 24, and 48 hours) through wound healing assays. Results show that 250 nM of MBQ-167 inhibits Rac and PAK activation by 50% as well as cell viability at both time points (48 and 96 hours). MBQ-167 (150 nM-500 nM) also blocked glioblastoma cell migration at 12, 24, and 48 hours. Taken together, these results confirm that MBQ-167 is a viable inhibitor in glioblastoma. Citation Format: Derealise Garcia Almedina, Nilmary Grafals-Ruiz, Suranganie Dharmawardhane, Anamaris Torres-Sanchez. The potential therapeutic effect of the Rac/Cdc42 inhibitor MBQ-167 in glioblastomain vitro [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 1586.
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