Abstract
Aim:
To investigate the anticancer mechanisms of triptolide, a diterpenoid isolated from the plant Tripterygium wilfordii Hook F, against human breast cancer cells and the involvement of the estrogen receptor-α (ERα)-mediated signaling pathway in particular.
Methods:
Human breast cancer ERα-positive MCF-7 cells and ERα-negative MDA-MB-231 cells were tested. PrestoBlue assay was used to evaluate the cell viability. The levels of ERα mRNA and protein were detected with real-time PCR and immunoblotting, respectively. Mouse models of MCF-7 or MDA-MB-231 xenograft tumors were treated with triptolide (0.4 mg·kg−1·d−1, po) or a selective estrogen receptor modulator tamoxifen (mg·kg−1·d−1, po) for 3 weeks, and the tumor weight and volume were measured.
Results:
Triptolide (5–200 nmol/L) dose-dependently inhibited the viability of both MCF-7 and MDA-MB-231 cells, with a more potent inhibition on MCF-7 cells. Knockdown of ERα in MCF-7 cells by siRNA significantly attenuated the cytotoxicity of triptolide, whereas overexpression of ERα in MDA-MB-231 cells markedly enhanced the cytotoxicity. Triptolide dose-dependently decreased the expression of ERα in MCF-7 cells and MCF-7 xenograft tumors. Furthermore, treatment of MCF-7 cells with triptolide inhibited the phosphorylation of ERK1/2 in dose- and time-dependent manners. In the mice xenografted with MCF-7 cells, treatment with triptolide or tamoxifen resulted in significant reduction in the tumor weight and volume. Similar effects were not obtained in the mice xenografted with MDA-MB-231 cells.
Conclusion:
The anticancer activity of triptolide against ERα-positive human breast cancer is partially mediated by downregulation of the ERα-mediated signaling pathway.
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Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (No 81001564, 81102887, 81274146, and 81320108029), the Natural Science Foundation of Jiangsu Province (No BK 2010433) and Beijing Nova Program (No Z141107001814061).
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Li, H., Pan, Gf., Jiang, Zz. et al. Triptolide inhibits human breast cancer MCF-7 cell growth via downregulation of the ERα-mediated signaling pathway. Acta Pharmacol Sin 36, 606–613 (2015). https://doi.org/10.1038/aps.2014.162
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DOI: https://doi.org/10.1038/aps.2014.162
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