HM-3-HSA exhibits potent anti-angiogenesis and antitumor activity in hepatocellular carcinoma.

HM-3-HSA is an antitumor fusion protein which improved the pharmacokinetics of HM-3. Previous studies reported that HM-3-HSA enhanced antitumor activity of HM-3 in melanoma cells. However, the efficacy and the mechanism of HM-3-HSA in hepatocellular carcinoma, especially its effect on tumor angiogenesis, have not been elucidated. Herein, we showed that HM-3-HSA significantly inhibited the H22 and SMMC-7721 tumor xenografts growth and tumor angiogenesis in vivo, indicating the antitumor activity exerted by HM-3-HSA was closely corrected with its potency on tumor angiogenesis. To investigate the anti-angiogenic mechanism, we evaluated the efficacy of HM-3-HSA in HUVECs in vitro. The results showed that multiple steps of tumor angiogenesis, including endothelial cell proliferation, migration, invasion and tube formation, were substantially inhibited by HM-3-HSA. Mechanism investigations revealed that HM-3-HSA could bind HUVECs via integrin αvß3 and α5ß1 and inhibited phosphorylation of the downstream protein kinases including FAK, Src and PI3 K. Our study was the first to report the activity of HM-3-HSA against hepatocellular carcinoma and tumor angiogenesis as well as the underlying mechanism by which HM-3-HSA to exert its anti-angiogenic activity.

Ferulic acid delayed amyloid ß-induced pathological symptoms by autophagy pathway via a fasting-like effect in Caenorhabditis elegans.

The amyloid ß (Aß) generation or aggregation plays a crucial role in Alzheimer's disease (AD). Autophagy agonists, which function as the clearance of Aß, could be the potential drug candidates against AD. In staple food crops, ferulic acid (FA) is an enormously copious and almost ubiquitous phenolic antioxidant. In the present study, FA significantly inhibited Aß-induced pathological symptoms of paralysis and hypersensitivity to exogenous serotonin, meanwhile restrained Aß monomers, oligomers, and deposits in AD C. elegans. FA increased the expression of autophagy reporter LGG-1 and enhanced autophagy flux. However, the autophagy inhibitors abolished the restrictive action of FA on the worm paralysis phenotype. According to these results, FA triggered autophagy and ameliorated Aß-induced pathological symptoms by the autophagy pathway. Moreover, FA activated the HLH-30 transcription factor to nuclear localization, which acts upstream of autophagy in fasted animals, reduced the level of lipids, but affected nor the growth of E. coli OP50, neither animal food intake behavior. These suggest that FA induced a fasting-like effect to activate the autophagy pathway. Additionally, FA ameliorated poly Q aggregations in Huntington's disease worm. Thus, FA could not only affect AD, broadly but also neurodegenerative diseases characterized by misfolded or aggregated proteins.