Jolkinolide B induces apoptosis in MCF-7 cells through inhibition of the PI3K/Akt/mTOR signaling pathway
- Authors:
- Hui-Yu Xu
- Zhi-Wei Chen
- Jin-Cai Hou
- Feng-Xia Du
- Ji-Cheng Liu
View Affiliations
Affiliations: Department of Immunology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, The Institute of Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China
- Published online on: October 31, 2012 https://doi.org/10.3892/or.2012.2113
-
Pages:
212-218
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Abstract
The aim of this study was to explore the molecular mechanisms of jolkinolide B (JB), which is extracted from the root of Euphorbia fischeriana Steud. In this study, we found that JB, a diterpenoid from the traditional Chinese medicinal herb, strongly inhibited the PI3K/Akt/mTOR signaling pathway. Furthermore, we evaluated the effects of JB on the proliferation and apoptosis of MCF-7 human breast cancer cells. Our results showed significant induction of apoptosis in MCF-7 cells incubated with JB. The viability of the MCF-7 cells was assessed by MTT assay. Flow cytometry was used to detect apoptosis and cell cycle analysis. Transmission electron microscopy (TEM) analysis was used to observe cell morphology. MCF-7 cells were subcutaneously inoculated into nude mice to study the in vivo antitumor effects of JB. The growth of MCF-7 cells was inhibited and arrested in the S phase by JB. The data showed significantly decreased tumor volume and weight in nude mice inoculated with MCF-7 cells. In addition, treatment with JB was able to induce downregulation of cyclinD1, cyclinE, mTOR, p-PI3K and p-Akt, and upregulation of PTEN and p-eIF4E. Collectively, JB-induced apoptosis of MCF-7 cells occurs through the PI3K/Akt/mTOR signaling pathway. Furthermore, the PI3K/Akt signaling cascade plays a role in the induction of apoptosis in JB-treated cells. These observations suggest that JB may have therapeutic applications in the treatment of cancer.
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