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Journal of Chinese Integrative Medicine ›› 2011, Vol. 9 ›› Issue (5): 533-538.doi: 10.3736/jcim20110511

• Original Experimental Research • Previous Articles     Next Articles

Effects of deguelin on proliferation and apoptosis of MCF-7 breast cancer cells by phosphatidylinositol 3-kinase/Akt signaling pathway

Zhao-hui Chu1,2, Xiao-hua Liang1,2(), Xin-li Zhou1,2, Ruo-fan Huang1,2, Qiong Zhan1,2, Jing-wei Jiang1,2   

  1. 1. Department of Oncology, Huashan Hospital, Fudan University, Shanghai 200040, China
    2. School of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Received:2010-12-18 Accepted:2010-12-27 Online:2011-05-20 Published:2011-05-15
  • Contact: Liang Xiao-hua

Objective: To study the effects of deguelin on proliferation and apoptosis of human breast cancer cell line MCF-7 and on phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.
Methods: After treatment with 0, 1, 5, 10, 15 and 20 μmol/L of deguelin for 6, 24, 48 and 72 hours, the proliferation inhibition rate of MCF-7 cells was measured by cell counting kit-8 assay. Apoptosis rate of MCF-7 cells was detected with Annexin V-fluorescein isothiocyanate/propidium iodide double staining by flow cytometry and the apoptotic morphology was observed under a transmission electron microscope. After treatment with 0, 1 and 5 μmol/L of deguelin for 6 hours, 5 proteins involved in the PI3K/Akt signaling pathway were examined by Western blot analysis.
Results: Deguelin at doses of 5, 10, 15 and 20 μmol/L inhibited the proliferation of MCF-7 cells at 6, 24, 48 and 72 hours. There was a significant difference in each group compared with the control group (P<0.01). The inhibitory effect was more marked with increasing concentration and duration of treatment. There were statistical differences (P<0.05) among 5, 10, 15 and 20 μmol/L groups. However, 1 μmol/L of deguelin had no obvious effects on the proliferation of MCF-7 cells at 6, 24, 48 and 72 hours, showing no significant difference compared with control group (P>0.05). Deguelin at doses of 5, 10, 15 and 20 μmol/L induced apoptosis of MCF-7 cells at 6 hours. There were significant differences (P<0.01) in the early and late apoptosis rate between the treated groups and the control group. The typical apoptotic MCF-7 cells were observed under the transmission electron microscopy. However, 1 μmol/L of deguelin had no apparent effect in inducing apoptosis of MCF-7 cells at 6 hours. After treatment with 5 μmol/L of deguelin for 6 hours the expression of phosphorylated phosphatase and tensin homologue deleted on chromosome 10 (PTEN) (Ser380), phosphorylated 3-phosphoinositide-dependent protein kinase 1 (PDK1) (Ser241), phosphorylated Akt (Thr308) and phosphorylated glycogen synthase kinase-3β (GSK-3β) (Ser9) proteins were significantly reduced in MCF-7 cells, while there was no significant change in the expression of total Akt protein. However, after treatment with 1 μmol/L of deguelin for 6 hours, there was no apparent change in the expression of these 5 proteins.
Conclusion: Deguelin can inhibit the phosphorylation of GSK-3β (Ser9) via inhibition of the phosphorylation of PTEN (Ser380) and PDK1 (Ser241) pathway, thus inducing apoptosis and inhibiting proliferation of MCF-7 cells.

Key words: deguelin, 1-phosphatidylinositol 3-kinase, Akt, cell proliferation, apoptosis, MCF-7 cell line, in vitro



Figure 1

A poptotic morphology of MCF-7 cells after culturing with deguelin for 6 h (Transmission electron microscopy, ×10 000)"

Figure 2

Expressions of PI3K/Akt signaling pathway proteins in MCF-7 cells after culturing with deguelin for 6 h GAPDH: glyceraldehyde-3-phosphate dehydrogenase; p-PTEN: phosphorylated phosphatase and tensin homologue deleted on chromosome 10; p-PDK1: phosphorylated 3-phosphoinositide-dependent protein kinase 1; p-GSK-3β: phosphorylated glycogen synthase kinase-3β."

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