Calycosin induces apoptosis in osteosarcoma cell line via ERβ‑mediated PI3K/Akt signaling pathways

Tian,Wei; Wang,Zhi‑Wei; Yuan,Bao‑Ming; Bao,Yong‑Ge

doi:10.3892/mmr.2020.11039

Calycosin induces apoptosis in osteosarcoma cell line via ERβ‑mediated PI3K/Akt signaling pathways

Authors:
- Wei Tian
- Zhi‑Wei Wang
- Bao‑Ming Yuan
- Yong‑Ge Bao
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Affiliations: Department of Orthopedics, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia Autonomous Region 028007, P.R. China
Published online on: March 26, 2020 https://doi.org/10.3892/mmr.2020.11039
Pages: 2349-2356
Copyright: © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have shown that calycosin, a natural phytoestrogen which is structurally similar to estrogen, inhibits proliferation and induces apoptosis in estrogen‑dependent cancer types via the estrogen receptor (ER)β‑induced inhibition of PI3K/Akt. Therefore, the aims of the present study were to investigate the effects of calycosin on human osteosarcoma (OS), and to examine the molecular mechanisms associated with ERβ. Human OS MG‑63 cells were treated with various concentrations of calycosin, and MTT and flow cytometry assays were used to assess the effects of calycosin on cellular proliferation and apoptosis. In addition, protein expression levels of ERβ, phosphorylated (p)‑PI3K, p‑Akt, cleaved poly (ADP‑ribose) polymerase 1 (PARP) and cleaved caspase‑3 were evaluated by western blot analysis. The present results suggested that calycosin inhibited proliferation and induced apoptosis in MG‑63 cells. Furthermore, increased ERβ expression was detected in OS MG‑63 cells treated with calycosin, and an ERβ inhibitor (PHTPP) reversed calycosin‑induced cytotoxicity and apoptosis. Moreover, phosphorylation levels of PI3K and Akt were significantly downregulated after calycosin treatment, whereas PHTPP reversed their phosphorylation. ERβ‑mediated PI3K/Akt downstream signaling pathways were found to influence the activity of poly (ADP‑ribose) polymerase 1 and caspase‑3. Thus, the present results indicated that calycosin inhibited proliferation and induced apoptosis in OS MG‑63 cells, and that these effects were mediated by ERβ‑dependent inhibition of the PI3K/Akt pathways.

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