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Isothiocyanate Iberin inhibits cell proliferation and induces cell apoptosis in the progression of ovarian cancer by mediating ROS accumulation and GPX1 expression - 18/06/21

Doi : 10.1016/j.biopha.2021.111533 
Ting-Ting Gong a, Qian Guo a, Xiao Li a, Tie-Ning Zhang b, Fang-Hua Liu c, Xin-Hui He c, Bei Lin a, , Qi-Jun Wu c,
a Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China 
b Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China 
c Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China 

Correspondence to: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang 110004, People’s Republic of China.Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University36 Sanhao StreetShenyang110004People’s Republic of China⁎⁎Correspondence to: Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang 110004, People’s Republic of China.Department of Clinical Epidemiology, Shengjing Hospital of China Medical University36 Sanhao StreetShenyang110004People’s Republic of China
En prensa. Pruebas corregidas por el autor. Disponible en línea desde el Friday 18 June 2021
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Abstract

Ovarian cancer (OC) is one of the most common gynecologic malignancies with poor survival rate, and Iberin is a member of isothiocyanate family with anti-tumor activity. However, the role of Iberin in OC development has not been reported yet. In this study, A2780 and OVCAR-3 cells were treated with gradient concentrations of Iberin to investigate the effect of Iberin on OC in vitro. Meanwhile, the in vivo tumorgenesis experiment was performed using female BALB/c nude mice treated with Iberin. Iberin inhibited cell proliferation, induced G2 cell cycle arrest and promoted cell apoptosis in OC cells. Besides, Iberin reduced GSH/GSSG level, enhanced ROS accumulation, and activated MAPK signaling in OC cells. More interestingly, ROS scavenger (NAC) compensated the anti-proliferative and pro-apoptotic effects of Iberin on OC cells, suggesting the involvement of ROS in the regulation of Iberin on OC cell growth. Notably, Iberin induced down-regulation of glutathione peroxidase-1 (GPX1), and over-expression of GPX1 reversed Iberin-mediated alterations in the proliferation, apoptosis and ROS accumulation of OC cells. The in vivo tumorgenesis study further evidenced the protection of Iberin against OC development. Besides, Iberin displayed a synergistic effect on the enhancement of chemo-sensitivity in OC cells. In summary, our study demonstrates the anti-tumor effect of Iberin on OC and its potential as a therapeutic agent against OC in the future.

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Graphical Abstract




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Highlights

Iberin inhibits cell proliferation and induces cell apoptotic death in OC cells.
Iberin plays anti-proliferative and pro-apoptotic role in OC cells by inducing ROS.
Iberin mediates proliferation, apoptosis and ROS accumulation of OC cells by GPX1.
Iberin inhibits the in vivo tumorgenesis of OC.
Iberin promotes chemo-sensitivity of OC cells.

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Keywords : Iberin, Ovarian cancer, Cell proliferation, Apoptosis, ROS accumulation, GPX1


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