Natural product‑derived icaritin exerts anti‑glioblastoma effects by positively modulating estrogen receptor β

Li,Xiaowen; Zhang,Weiwei; Liang,Lingli; Duan,Xiaoqun; Deng,Jianzhi; Zhou, Yuehan

doi:10.3892/etm.2020.8571

Natural product‑derived icaritin exerts anti‑glioblastoma effects by positively modulating estrogen receptor β

Authors:
- Xiaowen Li
- Weiwei Zhang
- Lingli Liang
- Xiaoqun Duan
- Jianzhi Deng
- Yuehan Zhou
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Affiliations: Department of Pharmacology, College of Pharmacy, Guilin Medical University, Guilin, Guangxi 541004, P.R. China, Department of Medical Oncology, The Affiliated Yantai Yuhuangding Hospital, Medical College of Qingdao University, Yantai, Shandong 264000, P.R. China, Guangxi Key Laboratory of Embedded Technology and Intelligent System, Guilin University of Technology, Guilin, Guangxi 541004, P.R. China
Published online on: February 27, 2020 https://doi.org/10.3892/etm.2020.8571
Pages: 2841-2850
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioblastoma is the most common malignancy of the central nervous system, and patients typically have a poor prognosis. Previous studies indicate a gender bias in the development of glioblastoma; women are at a lower risk compared with men, suggesting that estrogen may confer protective effects. Icaritin, a prenylflavonoid derivative from a Chinese herb of the Epimedium genus, selectively regulates the estrogen receptor (ER) and possesses anti‑cancer properties. The aim of the present study was to investigate the protective effects of icaritin on glioblastoma and its underlying mechanisms, with a particular focus on its association with the ER. The results demonstrated that icaritin inhibited the growth of C6 and U87‑MG glioblastoma cells in a dose‑ and time‑dependent manner. At a concentration of 12.5 µM, icaritin induced apoptosis, which was characterized by the increased expression of the cleaved forms of caspases 3, 7, 8 and 9 and poly (ADP‑ribose) polymerase, downregulation of BCL2 apoptosis regulator and upregulation of BCL2‑associated X, apoptosis regulator expression. Additionally, icaritin inhibited the migration of C6 and U87‑MG cells. The protein expression levels of matrix metalloproteinase (MMP)‑2 and MMP‑9 were also downregulated following icaritin treatment. Furthermore, icaritin treatment increased the expression of estrogen receptor (ER)β and the phosphatase and tensin (PTEN) homolog oncoprotein, thus reducing the expression of downstream targets of PTEN; protein kinase B (Akt) and phosphorylated Akt. Subsequent experiments demonstrated that icaritin cooperates with 17β‑estradiol to inhibit the growth of glioblastoma cells, and the inhibition of ERβ with the ERβ‑specific antagonist ICI 182,780, attenuated the anti‑glioblastoma effects of icaritin. In conclusion, the results of the present study demonstrate that the anti‑glioblastoma effects of icaritin may be mediated by its modulation of ERβ.

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