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.
View References
1
|
Ginsburg OM and Love RR: Breast cancer: a
neglected disease for the majority of affected women worldwide.
Breast J. 3:289–295. 2011. View Article : Google Scholar : PubMed/NCBI
|
2
|
McDermott SP and Wicha MS: Targeting
breast cancer stem cells. Mol Oncol. 5:404–419. 2010. View Article : Google Scholar : PubMed/NCBI
|
3
|
Laxmi Y, Elegbedea JA and Carpera SW:
Methyl jasmonate decreases membrane fluidity and induces apoptosis
via tumor necrosis factor receptor 1 in breast cancer cells.
Anticancer Drugs. 8:766–776. 2008.PubMed/NCBI
|
4
|
Shibani M, Natalya F, Andrea S, et al:
Hedgehog signaling and response to cyclopamine differ in epithelial
and stromal cells in benign breast and breast cancer. Cancer Biol
Ther. 6:674–683. 2006.PubMed/NCBI
|
5
|
Kumara S, Indrajit R, Anchooria RK, et al:
Targeted inhibition of hedgehog signaling by cyclopamine prodrugs
for advanced prostate cancer. Bioorg Med Chem. 6:2764–2768. 2008.
View Article : Google Scholar : PubMed/NCBI
|
6
|
Bara EE, Chaudhrya A, Lina A, et al:
Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like
cancer cells in glioblastoma. Stem Cells. 10:2524–2533. 2007.
View Article : Google Scholar : PubMed/NCBI
|
7
|
Li XL, Meng QH, Fan SJ, et al:
Adenovirus-mediated expression of UHRF1 reduces the
radiosensitivity of cervical cancer HeLa cells to
gamma-irradiation. Acta Pharmacol Sin. 4:458–466. 2009.PubMed/NCBI
|
8
|
Jiao Y, Ge CM, Meng QH, et al:
Adenovirus-mediated expression of Tob1 sensitizes breast cancer
cells to ionizing radiation. Acta Pharmacol Sin. 10:1628–1636.
2007. View Article : Google Scholar : PubMed/NCBI
|
9
|
Jiao Y, Ge CM, Meng QH, et al:
Dihydroartemisinin is an inhibitor of ovarian cancer cell growth.
Acta Pharmacol Sin. 7:1045–1056. 2007. View Article : Google Scholar : PubMed/NCBI
|
10
|
Somesh B and Alahari SK: miRNA control of
tumor cell invasion and metastasis. Int J Cancer. 6:1283–1290.
2010.
|
11
|
Nguyena HH, Lavrenovc SN, Sundara SN, et
al: 1-Benzyl-indole-3-carbinol is a novel indole-3-carbinol
derivative with significantly enhanced potency of
anti-proliferative and anti-estrogenic properties in human breast
cancer cells. Chem Biol Interact. 3:255–266. 2010. View Article : Google Scholar
|
12
|
Chen L, Mayer JA, Krisko TI, et al:
Inhibition of the p38 kinase suppresses the proliferation of human
ER-negative breast cancer cells. Cancer Res. 23:8853–8861. 2009.
View Article : Google Scholar : PubMed/NCBI
|
13
|
Li MW, Mruk DD, Cheng CY, et al:
Mitogen-activated protein kinases in male reproductive function.
Trends Mol Med. 15:159–168. 2009. View Article : Google Scholar : PubMed/NCBI
|