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Published on: September 13, 2017
Calycosin induces apoptosis in osteosarcoma cell line via ERβ‑mediated PI3K/Akt signaling pathways
Wei Tian1, Zhi-Wei Wang1, Bao-Ming Yuan1
1Department of Orthopedics, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia Autonomous Region 028007, P.R. China.
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.
Insights
Calycosin, a phytoestrogen, inhibits osteosarcoma cell growth and promotes apoptosis. This effect is mediated through estrogen receptor beta (ERβ) by inhibiting the PI3K/Akt signaling pathway.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Calycosin, a phytoestrogen, mimics estrogen and inhibits proliferation in estrogen-dependent cancers.
- Estrogen receptor beta (ERβ) plays a role in ERβ-induced inhibition of PI3K/Akt signaling.
Purpose of the Study:
- Investigate calycosin's effects on human osteosarcoma (OS) cells.
- Examine the molecular mechanisms involving ERβ in calycosin's action on OS cells.
Main Methods:
- Human OS MG-63 cells were treated with calycosin.
- MTT and flow cytometry assays assessed proliferation and apoptosis.
- Western blot analyzed protein expression of ERβ, p-PI3K, p-Akt, cleaved PARP, and cleaved caspase-3.
Main Results:
- Calycosin inhibited proliferation and induced apoptosis in MG-63 cells.
- ERβ expression increased with calycosin treatment; an ERβ inhibitor reversed these effects.
- Calycosin downregulated p-PI3K and p-Akt, with reversal by the ERβ inhibitor.
Conclusions:
- Calycosin inhibits osteosarcoma cell proliferation and induces apoptosis.
- These effects are mediated by ERβ-dependent inhibition of the PI3K/Akt pathway.
- ERβ influences downstream signaling of PARP1 and caspase-3, impacting cell fate.
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