In vitro: |
European Journal of Pharmacology, 2013, 714(1-3):261-273. | Sprengerinin C exerts anti-tumorigenic effects in hepatocellular carcinoma via inhibition of proliferation and angiogenesis and induction of apoptosis.[Reference: WebLink] | The multi-targeted therapy for liver cancer has been considered as a novel strategy to fight hepatocellular carcinoma.
METHODS AND RESULTS:
In this study, we first found that sprengerinin C, a naturally derived compound strongly suppressed tumor angiogenesis in human umbilical vein endothelial cells. A mechanism study revealed that sprengerinin C blocked vascular endothelial growth factor receptor 2-dependent phosphoinositide 3-kinase/Akt/mTOR/matrix metalloproteinase and p38 MAPK/matrix metalloproteinase pathways, two major pathways for tumor angiogenesis. Moreover, sprengerinin C inhibited vascular endothelial growth factor release, a vital event for early angiogenesis response, from hypoxic HepG-2/BEL7402 cells by suppressing hypoxia-inducible factor-1α transcriptional activity. Furthermore, sprengerinin C induced HepG-2/BEL7402 cell apoptosis by activating NADPH oxidase/reactive oxygen species-dependent caspase apoptosis pathway and suppressed HepG-2/BEL7402 cell growth through p53-mediated G2/M-phase arrest. Sprengerinin C also showed a significant anti-tumor effect in the nude mouse xenograft model of human hepatocellular carcinoma.
CONCLUSIONS:
These results provide new insights into development of potent candidate compounds for liver cancer through affecting multiple tumor progression steps of angiogenesis, apoptosis and proliferation. |
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