Cyclopamine is a novel Hedgehog signaling inhibitor with significant anti‑proliferative, anti‑invasive and anti‑estrogenic potency in human breast cancer cells
- Authors:
- Jun Che
- Fu‑Zheng Zhang
- Chao‑Qian Zhao
- Xu‑Dong Hu
- Sai‑Jun Fan
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Affiliations: Key Laboratory of Radiation Biology, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China, Department of Radiation Oncology, The Fourth Hospital Affiliated to Soochow University, Wuxi, Jiangsu 214062, P.R. China
- Published online on: February 18, 2013 https://doi.org/10.3892/ol.2013.1195
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Pages:
1417-1421
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Abstract
Stimulation of Hedgehog (Hh) signaling induces carcinogenesis or promotes cell survival in cancers of multiple organs. In epithelial cancer with aberrant Hedgehog activation, abrogation of Hedgehog signaling by cyclopamine, a naturally occurring Hedgehog‑specific small‑molecule inhibitor, causes profound inhibition of tumor growth. In the present study, cyclopamine displayed a significant potency in suppressing the proliferation of both estrogen‑responsive (MCF‑7) and estrogen‑independent (MDA‑MB‑231) human breast cancer cells. Cyclopamine induced a robust G1 cell cycle arrest and elicited notable effects on the expression of cyclin D1 through modulation of the MAPK/ERK signaling pathway. Cyclopamine also inhibited the invasive ability of both breast cancer cell lines by suppressing the expression levels of NF‑κB, MMP2 and MMP9 protein. Furthermore, in estrogen‑responsive MCF‑7 cells, cyclopamine significantly downregulated the production of estrogen receptor‑α protein. Our results implicate cyclopamine as a novel, potent inhibitor of human breast cancer proliferation and estrogen responsiveness that could potentially be developed into a promising therapeutic agent for the treatment of breast cancer.
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