Crocin inhibits proliferation and induces apoptosis through suppressing MYCN expression in retinoblastoma

Abstract

The pathogenetic mechanisms of retinoblastoma are still not yet fully elucidated, putting limits to efficacious treatment. Crocin is the main component of saffron, which exhibits significant antitumorigenic properties. The aim of this paper is to investigate the effect of crocin on retinoblastoma. The effects of crocin on the proliferation of human retinoblastoma cells were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell number assay, and colony formation assay. Cell apoptosis induced by crocin was measured by flow cytometry analysis. Cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 were tested by western blot analysis. The expression levels of MYCN were assessed by western blot and quantitative polymerase chain reaction and the stability of MYCN messenger RNA was determined by in vitro RNA degradation assays. We found that crocin significantly inhibited the cell proliferation and clonogenicity and induced cell apoptosis in Y79 and WERI-RB-1 cells. In addition, crocin treatment significantly reduced the expression and the stability of MYCN. Besides, overexpression of MYCN rescued the inhibitory effect of crocin in Y79 cells. Our findings suggest that crocin exhibits antitumorigenic effects in human retinoblastoma cell lines through a MYCN-dependent manner, which may provide guidance to logical therapeutic designs in prevention and treatment of retinoblastoma.

Keywords: MYCN; cleaved caspase-3; cleaved poly (ADP-ribose) polymerase; crocin; retinoblastoma.