Background:
A Chinese folk medicine plant Pleurospermum lindleyanum possesses pharmacological activities
of heat-clearing, detoxifying and preventing from hepatopathy, coronary heart disease, hypertension, and high altitude
sickness. We isolated and characterized its constituents to investigate its synergistic effects against human hepatoma
SMMC-7721 cells.
Objective:
The aim of this study was to explore the synergistic anti-cancer activities of isolates from P. lindleyanum with
5-FU on hepatoma SMMC-7721 cells in vitro and their primary mechanisms.
Methods:
Sequential chromatographic techniques were conducted for the isolation studies. The isolates structures were
established by spectroscopic analysis as well as X-ray crystallographic diffraction. Growth inhibition was detected by
MTT assay. The isobologram method was used to assess the effect of drug combinations. Flow cytometry and western
blot were used to examine apoptosis and protein expression.
Results:
A new coumarin (16), along with sixteen known compounds, were isolated from the whole plant of P.
lindleyanum and their structures were elucidated by spectroscopic methods. Four coumarins (2, 3, 5, and 16), two
flavonoids (8 and 9) and three phytosterols and triterpenes (12-14) were found to synergistically enhance the inhibitory
effect of 5-FU against SMMC-7721 cells. Among them, compounds 3 and 16 exhibited the best synergistic effects with
IC50 of 5-FU reduced by 16-fold and 22-fold possessing the minimum Combination Index (CI) 0.34 and 0.27. The
mechanism of action of combinations might be through synergistic arresting for the cell cycle at G1 phases and the
induction of apoptosis. Moreover, western blotting and molecular docking revealed that compounds 3 or 5 might promote
5-FU-induced apoptosis by regulating the expression of Caspase 9 and PARP.
Conclusion:
Constituents from P. lindleyanum may improve the treatment effectiveness of 5-FU against hepatocellular
carcinoma cells.
Protrusion-localized STAT3 mRNA promotes metastasis of highly metastatic hepatocellular carcinoma cells in vitro
