Apigenin inhibits tumor angiogenesis by suppressing microvesicle biogenesis

Apigenin regulates multiple pathways related to microvesicle biogenesis without affecting the expression of small Rho GTPase activator guanine nucleotide exchange factors (GEFs). However, apigenin can primarily targets ARHGEF1 protein, a GEF of the small GTPases, thereby inhibiting the activity of small G proteins such as Cdc42, which is essential in regulating the signaling for the release of microvesicles from tumor cells. Targeting ARHGEF1, apigenin effectively prevents tumor cells from releasing microvesicles. This, in turn, inhibits tumor angiogenesis related to VEGF90K transport on microvesicles, ultimately impeding tumor progression. To investigate the effect of apigenin on transcriptional regualtion, we performed gene expression profiling analysis using data obtained from RNA-seq of HCC-LM3 cells treated with or without apigenin.