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. 2015 Apr;29(2):132-8.
doi: 10.7555/JBR.27.20120115. Epub 2012 Dec 20.

Osthole inhibits proliferation of human breast cancer cells by inducing cell cycle arrest and apoptosis

Lintao Wang  1 , Yanyan Peng  2 , Kaikai Shi  2 , Haixiao Wang  3 , Jianlei Lu  2 , Yanli Li  1 , Changyan Ma  2
Affiliations

Osthole inhibits proliferation of human breast cancer cells by inducing cell cycle arrest and apoptosis

Lintao Wang et al. J Biomed Res. 2015 Apr.

Abstract

Recent studies have revealed that osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, a traditional Chinese medicine, possesses anticancer activity. However, its effect on breast cancer cells so far has not been elucidated clearly. In the present study, we evaluated the effects of osthole on the proliferation, cell cycle and apoptosis of human breast cancer cells MDA-MB 435. We demonstrated that osthole is effective in inhibiting the proliferation of MDA-MB 435 cells, The mitochondrion-mediated apoptotic pathway was involved in apoptosis induced by osthole, as indicated by activation of caspase-9 and caspase-3 followed by PARP degradation. The mechanism underlying its effect on the induction of G1 phase arrest was due to the up-regulation of p53 and p21 and down-regulation of Cdk2 and cyclin D1 expression. Were observed taken together, these findings suggest that the anticancer efficacy of osthole is mediated via induction of cell cycle arrest and apoptosis in human breast cancer cells and osthole may be a potential chemotherapeutic agent against human breast cancer.

Keywords: apoptosis; breast cancer; cell cycle; osthole; proliferation.

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Conflict of interest statement

The authors reported no conflict of interest.

Figures

Fig. 1
Fig. 1. Effects of osthole on the proliferation of MDA-MB 435 cells.*P < 0.05, **P < 0.01 vs. control (0 μ mol/L osthole)
Fig. 2
Fig. 2. Effects of osthole on the cell cycle distribution of MDA-MB 435 cells. MDA-MB 435 cells were treated with osthole for 36 hours. Cells were harvested and prepared for the cell cycle detection using flow cytometer as described in the Materials and Methods. Images are shown for one of three separate experiments. A: Control group. B: osthole 25 μmol/L. C: osthole 50 μmol/L. D: osthole 100 μmol/L.
Fig. 3
Fig. 3. Effects of osthole on the apoptosis of MDA-MB 435 cells. MDA-MB 435 cells were treated with osthole (0, 25, 50 and 100 μmol/L) for 36 hours. Cells were harvested and analyzed with annexin V and propidium iodide using flow cytometer as described in the Methods. A: Representative histograms of three separate experiments. B: Results of three separate experiments are shown. Values are expressed as mean±SD. **P < 0.01.
Fig. 4
Fig. 4. Effects of osthole on the expression of p53 and p21 as well as Cdk2 and cyclin D1. MDA-MB 435 cells were treated with osthole (0, 25, 50 and 100 μmol/L) for 36 hours. Cell lysates were immunoblotted with anti-p53 (A) anti-p21 (B) anti-Cdk2 (C) and anti-cyclin D1 (D) antibodies, respectively. β-actin served as loading control.
Fig. 5
Fig. 5. Effects of osthole on the levels of pro-caspase-3, PARP and pro-caspase-9. MDA-MB 435 cells were treated with osthole (0, 25, 50 and 100 μmol/L) for 36 hours. Cell lysates were immunoblotted with anti-pro-caspase-3 (A) anti-PARP (B) and anti-pro-caspase-9 (C) antibodies, respectively. β-actin served as loading control.
Fig. 6
Fig. 6. Effects of osthole on the levels of Bcl-2 (A) and Bax (B). MDA-MB 435 cells were treated with osthole (0, 25, 50 and 100 μmol/L) for 36 hours. Cell lysates were immunoblotted with anti-Bcl-2 and anti-Bax antibodies, respectively. β-actin served as loading control.
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