Anticancer activity of sulforaphane against human hepatoblastoma cells involves apoptosis, autophagy and inhibition of β-catenin signaling pathway.

INTRODUCTION

Sulforaphane is an active isothiocyanate and has been reported to exhibit many pharmacological and biological activities including anticancer activity. The current study was undertaken to examine its anticancer activity against human hepatoblastoma.

MATERIAL AND

METHODS

MTT and clonogenic assays were used to assess the antiproliferative effects of sulforaphane. Annexin V/PI staining and immunofluorescence microscopy were used to monitor the induction of apoptosis. GFP-LC3 transfection and fluorescence microscopy were used to investigate the induction of autophagy. Cell migration and invasion were assessed through wound healing and transwell chamber assay. Protein expression was determined by western blot analysis.

RESULTS

The results indicated that sulforaphane induced antiproliferative effects on the hepatoblastoma cell lines and exhibited an IC50 of 10 μM against the Hepu1 and HepU2 cells as compared to the IC50 of 90 μM against the normal THLE-2 cells. The antiproliferative effects were observed to be mediated via apoptosis which was accompanied by upregulation of Bax and suppression of Bcl-2 together with activation of caspase-3 and PARP cleavage. Sulforaphane also induced autophagy and the β-catenin signaling pathway. In addition, cell migration and cell invasion of the hepatoblastoma cells were also suppressed upon sulforaphane treatment.

CONCLUSIONS

The results indicated that sulforaphane is a potential anticancer agent and may be considered as a lead molecule in the development of hepatoblastoma chemotherapy.