Abstract 1864: Baicalein attenuates endometrial cancer growth by suppressing the ARF6

Abstract

Abstract Using mass spectrometry-based proteomics, we have previously shown enhanced expression of the Adenosine diphosphate-Ribosylation Factor-6 (ARF6) in endometrial cancer cell lines compared to immortalized EM-E6/E7-TERT endometrial epithelial cells. ARFs belong to the RAS superfamily of small GTPases. ARF family proteins are activated by Guanine nucleotide Exchange Factors (GEFs) and inactivated by GTPase-Activating Proteins (GAPs). When active, they bind effectors, which mediate downstream functions. ARF6 localized on the plasma membrane plays a role in actin cytoskeleton dynamics and endocytic recycling. Dysregulation of expression and/or activity of ARF6 has been associated with enhanced cell migration, invasion, and proliferation in several types of cancer. Knockdown of ARF6 significantly inhibited the invasiveness of the cancer cells. There is a critical need for novel promising anticancer agents with lesser side effects and higher efficacy. Baicalein, extracted from the roots of the Chinese herb Huang Qin (Scutellaria baicalensis), showed a significant anticancer impact on many human cancers. However, the specific molecular mechanisms are still nebulous. Endometrial cancer cell lines were exposed to different concentrations of baicalein for 24 to 120 h. The effect on cell proliferation and invasion was determined utilizing MTS and Boyden chamber assays, respectively. The baicalein induced a dose and time-dependent reduction in cell viability. The invasiveness of cells was attenuated by baicalein. Furthermore, the anticancer effects were mediated by decreased ARF6, Rac1, and PAK1 expression in baicalein-treated cancer cells. In summary, the data reveal that suppression of ARF6 could reduce the invasive potential of endometrial cancer by modulating the major downstream effectors Rac1 and PAK1. Citation Format: Latoya Mcglorthan, Viqar Syed. Baicalein attenuates endometrial cancer growth by suppressing the ARF6 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1864.