Cyclopamine is an antagonist of the Hedgehog (Hh) pathway, demonstrating an IC50 of 46 nM in cell assays focused on the Hh pathway. Additionally, it selectively targets and inhibits Smo[1].
体内研究
Cyclopamine treatment results in the sustained regression of xenograft tumors, with complete regression observed within 12 days in treated animals[2].
Administration of Cyclopamine (1.2 mg) inhibits the development of tumors from human pancreatic adenocarcinoma cells transplanted into nude mice[3].
体外研究
Utilizing small molecule inhibitors of the Hh pathway, such as HhAntag and Cyclopamine, which both interact with Smo, has been shown to lead to tumor remission in a genetic mouse model for medulloblastoma[1].
Functioning as a Hedgehog (Hh) pathway antagonist, Cyclopamine impedes cell proliferation. Its inhibitory effect on the Hh pathway activity and the growth of digestive tract tumor cell lines, at a concentration of 3 μM, is linked to the level of PTCHmRNA expression[2].
As a steroidal alkaloid, Cyclopamine disrupts Hh signaling by directly binding to Smo[3].
Cyclopamine/环巴胺 细胞实验
Cell Line
Concentration
Treated Time
Description
References
786-0 cells
20 μM
5 days
Inhibited cell proliferation, reduced cell count by 80%
Mol Cancer. 2009 Dec 16;8:123.
786-0 cells
40 μM
5 days
Inhibited cell proliferation, reduced cell count by 90%
Mol Cancer. 2009 Dec 16;8:123.
hepatocytes
5 µM
24 h
To assess the direct effects of Cyclopamine on hepatocyte proliferative activity, results showed that Cyclopamine significantly inhibited BrdU incorporation in hepatocytes
Hepatology. 2010 May;51(5):1712-23.
mouse embryonic stem cells (mESCs)
5 µM
5 days
Induction of mouse embryonic stem cells into mesodermal lineage, results showed successful differentiation of mESCs into mesodermal cells under 3D culture conditions.
Sci Adv. 2017 May 12;3(5):e1602875.
PLC/PRF/5 and Huh7 cells
20 µM
Cyclopamine inhibited the expression of Smo and Gli1 and the stimulatory effect of rhSCUBE1 on HCC cells.
J Transl Med. 2022 Nov 8;20(1):520.
T21-iPSCs
400 ng/ml
12-14 days
For glutamatergic neuron differentiation from neural stem cells
Stem Cells Transl Med. 2017 Jun;6(6):1465-1476.
MATH1-GFP cells
10 µM
40 h
To investigate the effect of SHH pathway blockade on the cell division modes of GNPs, results showed that cyclopamine treatment increased the number of MATH1 and DCX double-positive cells and DCX-positive cells, indicating that cyclopamine inhibited non-terminal symmetric divisions and enhanced asymmetric divisions and terminal neuronal symmetric divisions.
Stem Cell Reports. 2015 Nov 10;5(5):816-828.
Human colon cancer epithelial cells
1-10 μM
48 h
Cyclopamine treatment reduced cell proliferation and increased apoptosis, indicating the essential role of HH-GLI signaling in colon cancer cells.
EMBO Mol Med. 2009 Sep;1(6-7):338-51.
Cyclopamine/环巴胺 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
KA-induced neurodegeneration model
Oral
30 mg/kg
Twice daily for 3 days, then once daily for 5 days
Inhibition of SHH/Gli signaling reduces cell proliferation in KA-induced neurodegeneration.
Glia. 2014 Oct;62(10):1595-607
Mice
Partial hepatectomy model
Intraperitoneal injection
15 mg/kg
Daily until the end of the experiment
To evaluate the effects of Cyclopamine on liver regeneration, results showed that Cyclopamine significantly inhibited the proliferation of hepatocytes and ductular cells, and reduced liver regeneration mass and survival rate
Cyclopamine partially inhibited the promotion of HCC tumor progression by CAFs.
J Transl Med. 2022 Nov 8;20(1):520.
Mice
Math1-GFP;Dcx-DsRed;Patched+//C0 mice
Intraperitoneal injection
10 mg/kg
Every 3 days, from E16 to P21
To investigate the effect of SHH pathway blockade on the cell division modes of GNPs, results showed that cyclopamine treatment decreased the number of MATH1-positive cells and increased the number of DCX-positive and MATH1/DCX double-positive cells, indicating that cyclopamine reversed the shift from asymmetric to symmetric divisions.
Stem Cell Reports. 2015 Nov 10;5(5):816-828.
Nude mice
Human colon cancer xenograft model
Intratumoral injection
10 mg/kg
Twice daily, continuous treatment
Cyclopamine treatment inhibited the growth of human colon cancer xenografts, indicating the critical role of HH-GLI signaling in tumor growth.
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