Mechanism study of isoflavones as an anti-retinoblastoma progression agent
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Qifeng Wu1, He Bai2, Chu-Long Huang3, Yongming Zhang1,4, Xiayun Zeng4, Huan Wan1, Wen Zuo5, Hai-Ying Wang3, Yi-Xin Zeng1,5,6,7 and Yan-Dong Wang3
1 National Cancer Center /Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
2 Department of Drug and Cosmetics Registration (Department of TCMs and Ethno- Medicines Supervision), China Drug and Food Administration, Beijing, P. R. China
3 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P. R. China
4 Guangdong Wholewin Technology Ltd., Foshan, P. R. China
5 Beijing Hospital, Beijing, P. R. China
6 Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China
7 State Key Laboratory of Oncology in Southern China, Guangzhou, P. R. China
Yi-Xin Zeng, email:
Yan-Dong Wang, email:
Keywords: isoflavones; retinoblastoma; mTOR pathway; cyclin E1
Received: March 28, 2017 Accepted: June 27, 2017 Published: July 18, 2017
Isoflavones, bioactive soy compounds, are known to exhibit anticancer activities. The present study investigated the anticancer activities of isoflavones on human retinoblastoma Y79 cellsin 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.
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