Cucurbitacin E (CuE), a highly oxygenated tetracyclic triterpene from Cucurbitaceae, has shown to exhibit potent cytotoxic and anti-proliferative properties against several human cancer cells. However, the underlying effects and mechanisms of CuE regarding hepatocellular carcinoma (HCC) have not been well understood. In the current study, unbiased RNA-sequencing (RNA-seq) and bioinformatics analysis was applied to elucidate the underlying molecular mechanism. CuE could significantly inhibit cell proliferation and migration of Huh7 cells, meanwhile CuE exhibited potent anti-angiogenic activity. RNA-seq analysis revealed that CuE negatively regulated 241 differentially expressed genes (DEGs) involved in multiple processes including cytoskeleton formation, angiogenesis and focal adhesion. Further analysis revealed that CuE effectually regulated diversified pharmacological signaling pathways such as MAPKs and JAK-STAT3. Our findings demonstrated the role of CuE in inhibiting proliferation and migration, providing an insight into the regulation of multiple signaling pathways as a new paradigm for anti-cancer treatment strategy.

Background: Histone post-translational modifications (PTMs) are involved in various biological processes such as transcriptional activation, chromosome packaging, and DNA repair. Previous studies mainly focused on PTMs by directly targeting histone-modifying enzymes such as HDACs and HATs.

Three previously undescribed biflavonoids, oxytrodiflavanone A (1), and oxytrochalcoflavanones A,B (2,3), were isolated from the aerial part of Oxytropis chiliophylla, together with their putative biosynthetic monomers, i.e., (2S)-5,7-dihydroxyflavanone (4), (2S)-7-hydroxyflavanone (5), and 2′,4′-dihydroxychalcone (6). The structures of these compounds were elucidated by a combination analysis of spectroscopic data. The cytotoxic activities of all the isolated compounds against PC-3 human prostate cancer cell line are also presented.