Suppression of ovarian cancer -related angiogenesis processes by cannabis extract fraction in vascular endothelial cells is associated with reduced F-actin and focal adhesion points reorganization

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Angiogenesis, the growth of new vessels from existing ones to supply oxygen and nutrients requirement for tissue, is essential for tumor growth and development. Cannabis sativa extract fraction (F7) was shown previously to be cytotoxic to ovarian cancer (OC) cells. Here we examined the effect of F7 on angiogenesis-related processes in HUVEC cells. Gene expression profiles were determined by quantitative PCR. Microscopy was used to determine actin arrangement and protein localization, a scratch and sprouting assay to determine cell migration and sprouting, respectively. Western blotting was used to determine protein levels . F7 treatment reduced HUVEC cell migration and sprouting, yet increased VEGF expression in HUVEC and OC cells. HUVEC sprouting and expression of regulatory and structural components of F-actin and focal adhesion point reorganization were increased by co-culturing of HUVEC with OC cells. F7 treatment reduced in HUVEC gene and protein expression related to F-actin and focal adhesion point reorganization. Confocal microscopy verified the reduction in stress fiber and focal adhesion points formation at protruding edges of the cells. Despite the increase in VEGF expression, F7 treatment reduced in vitro angiogenesis-related processes induced by OC cells in HUVEC. F7 suppressed F-actin and focal adhesion point reorganization, necessary for endothelial cell migration and sprouting. • F7 treatment increases VEGF gene expression in vascular endothelial cells (HUVEC) and ovarian cancer cells (OC). • F7 treatment reduces HUVEC cell migration and OC-induced sprouting. • F7 treatment reduces HUVEC F-actin and focal adhesion point-related gene expression and their reorganization, necessary for endothelial cell migration and sprouting. • Since angiogenesis is a vital process in solid tumor development, F7 treatment may be applicable as an anti-angiogenesis agent.

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