Evaluation of Anti-tumor and Chemoresistance-lowering Effects of Pectolinarigenin from Cirsium japonicum Fisch ex DC in Breast Cancer
Purpose: To investigate the antitumor and chemoresistance-lowering effects of pectolinarigenin on breast cancer cells.
Methods: Pectolinarigenin was purified by a combination of silica gel and Sephadex LH-20 column chromatography from ethanol extracts of the aerial parts of C. japonicum DC. Breast cancer selfrenewal properties were tested by colony formation and tumor sphere formation assays. Thereafter, real-time polymerase chain reaction (PCR) was used to detect breast cancer stem cell markers. Furthermore, the effect of pectolinarigenin on breast cancer cell was evaluated by chemoresistance using 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Finally, tumor formation in nude mice was used to test the effect of pectolinarigenin on tumorigenicity of breast cancer cells in vivo.
Results: The results showed that pectolinarigenin, extracted from Cirsium japonicum Fisch. ex DC., inhibited tumor cell self-renewal in MCF-7 breast cancer cells. Pectolinarigenin (25 μM) caused significant inhibition of colony formation (61.23 %, p < 0.001) and tumor sphere formation (59.49 %, p < 0.01) in MCF-7. The inhibitory effects were associated with changes in breast cancer stem cell markers. Treatment of breast cancer cells with pectolinarigenin reduced the chemoresistance of the cells to doxorubicin. At the same time, mRNA expression of chemoresistance genes (ATP binding cassette subfamily G member 2, ABCG2 and ATP binding cassette subfamily B member 1, MDR1) was repressed by pectolinarigenin. The inhibition efficiency of MDR1 and ABCG2 by 10 μM pectolinarigenin treatment was about 59.29 (p < 0.01) and 46.48 % (p < 0.01), respectively. Furthermore, pectolinarigenin reduced tumor mass in nude mice xenograft model.
Conclusion: Pectolinarigenin inhibits breast cancer stem cell-like properties and lowers the chemoresistance of the cancer cells to chemotherapy. The results provide an insight into the mechanism of the anti-breast tumor effects and an experimental basis for the use of pectolinarigenin to enhance treatment of patients with breast cancer.
Keywords: Pectolinarigenin, Cancer stem cells, Breast cancer, Chemoresistance, Cirsium japonicum Fisch. ex DC
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