Bauerenol inhibits proliferation, migration and invasion of retinoblastoma cells via induction of apoptosis, autophagy and cell cycle arrest

Abstract

Purpose: To determine the anticancer effects of bauerenol on human retinoblastoma cells. Methods: The effect of bauerenol on cell proliferation was evaluated using 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay, while cancer cell migration and invasion were determined by Transwell assay. Apoptosis of retinoblastoma cells was assessed by Annexin VFITC/PI staining procedure. Autophagy was evaluated using TEM, while cell cycle was studied by flow cytometry. Results: Bauerenol significantly inhibited the proliferation of retinoblastoma cells, with a half-maximal inhibitory concentration (IC50) of 10 μM (p < 0.05). However, bauerenol exhibited a comparatively lower antiproliferative effect on normal paediatric retina cells, with a higher IC50 of 100 μM. Annexin V/PI staining results revealed that the antiproliferative effect of bauerenol was due to apoptotic cell death. The proportion of apoptotic SORB-50 cells increased from about 4 % in control to about 19 % on exposure to 20 μM bauerenol. Western blot assay showed marked up-regulation of LC3B II protein, indicating autophagy. Cell cycle analysis showed that the arrest of SO-RB50 cells at the G2/M phase of the cell cycle markedly contributed to the antiproliferative effects of bauerenol. Moreover, the migration and invasion of SO-RB50 cells were suppressed by bauerenol (p < 0.05). Conclusion: These results indicate that bauerenol suppresses the growth of retinoblastoma cells. Therefore, it may be a beneficial lead molecule for the development of a suitable agent for the treatment of retinoblastoma. Keywords: Retinoblastoma; triterpenoid; anticancer; apoptosis; autophagy; migration; invasion; metastasis