Pectolinarigenin flavonoid exhibits selective anti-proliferative activity in cisplatin-resistant hepatocellular carcinoma, autophagy activation, inhibiting cell migration and invasion, G2/M phase cell cycle arrest and targeting ERK1/2 MAP kinases.

PURPOSE

The main purpose of the present research article was to investigate the anticancer properties of pectolinarigenin flavonoid in cisplatin-resistant hepatocellular carcinoma cells (SK-HEP-1) and normal liver cells (AML-12), along with examining its effects on autophagy, cell migration and invasion, cell cycle arrest and ERK1/2 MAP signalling pathways.

METHODS

Antiproliferative effects in cancer and normal cells were assessed by MTT cell viability assay. Cell autophagy effects were studied by electron microscopy as well as western blot. Effects on cell cycle were evaluated by flow cytometry using Annexin V/propidium iodide (PI) staining. Transwell migration assay and in vitro wound healing assay were performed to study the effects on cell migration and invasion, respectively.

RESULTS

The results indicated that pectolinarigenin inhibited significantly the growth of the SK-HEP-1 liver cancer cells and exhibited an IC50 of 10 µM, while against normal cells the cytotoxic effects were much less pronounced. Further, it was observed that the anticancer effects of pectolinarigenin were due to induction of autophagy which was also associated with upregulation of the expression of Beclin-1, LC3-I and LC3-II. Transmission electron microscopy showed the formation of autophagosomes and vesicles. Pectolinarigenin also caused arrest of the SK-HEP-1 cells at the G2/M-phase of the cell cycle. Wound healing and transwell assays showed pectolinarigenin suppressed the migration and invasive potential of the SK-HEP-1 cells.

CONCLUSIONS

The present study revealed that pectolinarigenin exhibits antitumor activity in SK-HEP-1 liver cancer cells via multiple mechanisms and may prove promising in the development of systemic therapy for liver cancer.