Osthole inhibits the proliferation of breast cancer MCF-7 cells via activating peroxisome proliferator-activated receptor γ

Abstract

Objective To investigate the effect of osthole on the proliferation and apoptosis of breast cancer cell line MCF-7 and its potential mechanisms. Methods Breast cancer cell line MCF-7 was treated by osthole 0, 25, 50, 100, 150 and 200 μmol/L respectively. MTT method was used to detect cell survival rate. HE staining was used to observe morphological changes, Annexin V-PI flow cytometry was used to analyze cell apoptosis, and RT-PCR and Western blot method were used to detect the mRNA and protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and farnesoid X receptor (FXR), respectively. Results MTT assay showed that strong cytotoxicity of cell line MCF-7 was induced after administration of osthole for 72 h in a dose-dependent manner. Especially, the maximum inhibitory rate, 73.0 % appeared in the 200 μmol/L group. HE staining showed that the number of MCF-7 cells decreased, hyperchromatic nuclei and apoptotic bodies appeared after treatment with osthole for 72 h in a significant dose-effect manner. Flow cytometric analysis revealed that osthole could induce extensive apoptosis in MCF-7 cultures after treatment for 72 h compared with normal group (P<0.05, P<0.01). In particular, when the concentration of osthole reached 50 μmol/L, the proportion of early apoptotic cells was significantly increased in a dose-dependent manner (P<0.01), especially. The maximum apoptosis rate (46.2±9.0) % appeared in the 200 μmol/L group, which was consistent with the results obtained from MTT assays. Moreover, osthole could significantly increased PPARγ and FXR mRNA and protein expressions (P<0.01). Conclusion These data suggest that osthole could inhibit the proliferation of breast cancer MCF-7 cells and promote its apoptosis, which might be associated with the regulation of PPARγ and FXR-mediated target genes involved in cell growth and metabolism. Key words: Osthole; Breast neoplasms; MCF-7 cells; Peroxisome proliferator-activated receptor γ; Farnesoid X receptor