Mechanism study of isoflavones as an anti-retinoblastoma progression agent.

Wen Zuo,Yan-Dong Wang,Yongming Zhang,He Bai,Chu-Long Huang,Hai-Ying Wang,Qifeng Wu,Yi-Xin Zeng,Xiayun Zeng,Huan Wan

doi:10.18632/oncotarget.19365

Abstract

Isoflavones, bioactive soy compounds, are known to exhibit anticancer activities. The present study investigated the anticancer activities of isoflavones on human retinoblastoma Y79 cells in vitro and in vivo. An MTT cell viability assay showed that the half maximal inhibitory concentration value of isoflavones against human retinoblastoma Y79 cells is 1.23 ± 0.42 μmol/l. Flow cytometry analysis indicated that isoflavones blocked G1/S progression. Western blot analysis demonstrated that the mammalian target of rapamycin (mTOR) pathway in Y79 cells was inhibited by isoflavones, with a concomitant decrease in cyclin E1, which accounted for the isoflavone-mediated G1 phase arrest. Isoflavones also inhibited human retinoblastoma growth in vivo; western blot analysis showed inhibition of mTOR and downregulation of cyclin E1 in an isoflavone-treated xenograft mouse model. Together, these results illustrate that isoflavones inhibit retinoblastoma tumour growth in vitro and vivo and that inactivation of the mTOR pathway and downregulation of cyclin E1 is involved in this action. The results of this study suggest that isoflavones could be tested as promising anti-retinoblastoma agent.

Highlights

Retinoblastoma is the most commonly occurring intraocular malignant tumour in infants and young children and originates from photoreceptor precursor cells [1]
A study revealed that activation of mammalian target of rapamycin (mTOR) could modulate some molecules via retinoblastoma protein phosphorylated, which told us the mTOR signal pathway may be directly related to some retinoblastoma proteins [23]; another research focused on RY-2f, a chemically synthesized isoflavone analog, that could inhibit ovarian tumorigenesis
We investigated whether there were anticancer activities of isoflavones in human retinoblastoma Y79 cells or not, and we primarily studied its effects on the mTOR pathway in vitro and vivo

Summary

Introduction

Retinoblastoma is the most commonly occurring intraocular malignant tumour in infants and young children and originates from photoreceptor precursor cells [1]. Daidzein, and glycitein are three major isoflavones which have some anti-cancer potential activities [6]. Isoflavones are helpful in the treatment of certain cancers by inhibiting tyrosine kinase activity and regulating Akt, mitogen-activated protein kinase and other signalling pathways [13,14,15,16,17]. The mTOR pathway is commonly deregulated in human malignancies [21], including retinoblastoma [22]. Scientists in this study demonstrated that the mechanism of anti-cancer role was through PI3K/Akt/mTOR signaling pathway [24]. These clues reminded us that isoflavones may be efficient to retinoblastoma

Methods

Results

Conclusion