Original Article
Acta Pharmacologica Sinica 35, 814-824 (June 2014) | doi:10.1038/aps.2014.15
Abrus agglutinin suppresses human hepatocellular carcinoma in vitro and in vivo by inducing caspase-mediated cell death
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Abstract
Aim:
Abrus
agglutinin (AGG) from the seeds of Indian medicinal plant Abrus
precatorius belongs to the class II ribosome inactivating protein
family. In this study we investigated the anticancer effects of AGG
against human hepatocellular carcinoma in vitro and in vivo.
Methods:
Cell
proliferation, DNA fragmentation, Annexin V binding,
immunocytofluorescence, Western blotting, caspase activity assays and
luciferase assays were performed to evaluate AGG in human liver cancer
cells HepG2. Immunohistochemical staining and TUNEL expression were
studied in tumor samples of HepG2-xenografted nude mice.
Results:
AGG
induced apoptosis in HepG2 cells in a dose- and time-dependent manner.
AGG-treated HepG2 cells demonstrated an increase in caspase 3/7, 8 and 9
activities and a sharp decrease in the Bcl-2/Bax ratio, indicating
activation of a caspase cascade. Co-treatment of HepG2 cells with AGG
and a caspase inhibitor or treatment of AGG in Bax knockout HepG2 cells
decreased the caspase 3/7 activity in comparison to HepG2 cells exposed
only to AGG. Moreover, AGG decreased the expression of Hsp90 and
suppressed Akt phosphorylation and NF-κB expression in HepG2 cells.
Finally, AGG treatment significantly reduced tumor growth in nude mice
bearing HepG2 xenografts, increased TUNEL expression and decreased CD-31
and Ki-67 expression compared to levels observed in the untreated
control mice bearing HepG2 cells.
Conclusion:
AGG
inhibits the growth and progression of HepG2 cells by inducing
caspase-mediated cell death. The agglutinin could be an alternative
natural remedy for the treatment of human hepatocellular carcinomas.
