Andrographolide Inhibits Human Hepatoma-Derived Hep3B Cell Growth through the Activation of c-Jun N-Terminal Kinase

Abstract

Andrographolide (Andro) is a potentially anti-inflammatory diterpenoid lactone isolated from the traditional herbal medicine Andrographis paniculata, which has been effectively used for the treatment of infection, inflammation, cold, fever and diarrhea in China for centuries. In the current study, we found that Andro significantly decreased the number of surviving hepatoma-derived Hep3B cells in the MTT assay and induced cell apoptosis. Further study showed that Andro induced activation of mitogen-activated protein kinases (MAPKs) including p38 kinase, c-Jun N-terminal kinase (JNK) and extracellular signal-related kinases (ERK1/2), but had no significant effect on caspase-3, Bcl-xL and Bcl-2, which are apoptosis-related proteins. Moreover, inhibition of JNK activation partially rescued the toxic effect of Andro on Hep3B cells. Therefore, our results indicate that the JNK signaling pathway plays an important role in the toxic effect of Andro on Hep3B cells.

Abbreviations

Andro:andrographolide

CDK:cyclin-dependent kinase

ELISA:enzyme-linked immunosorbent assay

ERK1/2:extracellular signal-related kinases

FBS:fetal bovine serum

HCC:hepatocellular carcinoma

HPLC:high pressure liquid chromatography

JNK:c-Jun N-terminal kinase

MAPK:mitogen-activated protein kinase

MEM:modified Eagle's medium

RTKs:receptor tyrosine kinases

Key words

Andrographolide - hepatoma-derived Hep3B cells - mitogen-activated protein kinase - c-Jun N-terminal kinase - caspase - Bcl-2 - Andrographis paniculata - Acanthaceae

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