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Atractylochromene Is a Repressor of Wnt/β-Catenin Signaling in Colon Cancer Cells.

Shim AR, Dong GZ, Lee HJ, Ryu JH - Biomol Ther (Seoul) (2015)

Bottom Line: The active compound was purified by activity-guided purification and the structure was identified as 2,8-dimethyl-6-hydroxy-2-(4-methyl-3-pentenyl)-2H-chromene (atractylochromene, AC).Furthermore, AC inhibits proliferation of colon cancer cell.Taken together, AC from A. macrocephala might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul 140-742.

ABSTRACT
Wnt/β-catenin signaling pathway was mutated in about 90% of the sporadic and hereditary colorectal cancers. The abnormally activated β-catenin increases the cancer cell proliferation, differentiation and metastasis through increasing the expression of its oncogenic target genes. In this study, we identified an inhibitor of β-catenin dependent Wnt pathway from rhizomes of Atractylodes macrocephala Koidzumi (Compositae). The active compound was purified by activity-guided purification and the structure was identified as 2,8-dimethyl-6-hydroxy-2-(4-methyl-3-pentenyl)-2H-chromene (atractylochromene, AC). AC suppressed β-catenin/T-cell factor transcriptional activity of HEK-293 reporter cells when they were stimulated by Wnt3a or inhibitor of glycogen synthase kinase-3β. AC down-regulated the nuclear level of β-catenin through the suppression of galectin-3 mediated nuclear translocation of β-catenin in SW-480 colon cancer cells. Furthermore, AC inhibits proliferation of colon cancer cell. Taken together, AC from A. macrocephala might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer.

No MeSH data available.


Related in: MedlinePlus

Atractylochromene inhibits β-catenin signaling pathway in SW-480 cells. SW-480 cells were treated with 20 μg/ml of atractylochromene for the indicated time, and cells were harvested to prepare nuclear and cytosolic fractions (A), and whole cell lysates (B). Relative expression levels of target proteins were detected by western blot analysis.
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f3-bt-23-26: Atractylochromene inhibits β-catenin signaling pathway in SW-480 cells. SW-480 cells were treated with 20 μg/ml of atractylochromene for the indicated time, and cells were harvested to prepare nuclear and cytosolic fractions (A), and whole cell lysates (B). Relative expression levels of target proteins were detected by western blot analysis.

Mentions: To further confirm the inhibitory effect of AC on Wnt/β-catenin signaling pathway, β-catenin constitutively activated SW-480 colon cancer cell line were used. Treatment of AC (20 μg/ml) decreased the nuclear level of β-catenin in SW-480 cells in a time-dependent manner. But the levels of β-catenin in cytosol and whole cell lysate were not affected by AC (Fig. 3A and 3B). And a target gene of β-catenin, cyclin D1 was decreased by treatment of AC in SW-480 cells. The level of galectin-3, one of the β-catenin nuclear translocation modulators, was also decreased in nuclear of AC-treated SW-480 cells, but not in cytosolic fraction and whole cell lysates (Fig. 3A, B). These data indicate that AC inhibits Wnt/β-catenin signaling pathway through modulating the nuclear translocation of β-catenin and galectin-3 in colon cancer cells.


Atractylochromene Is a Repressor of Wnt/β-Catenin Signaling in Colon Cancer Cells.

Shim AR, Dong GZ, Lee HJ, Ryu JH - Biomol Ther (Seoul) (2015)

Atractylochromene inhibits β-catenin signaling pathway in SW-480 cells. SW-480 cells were treated with 20 μg/ml of atractylochromene for the indicated time, and cells were harvested to prepare nuclear and cytosolic fractions (A), and whole cell lysates (B). Relative expression levels of target proteins were detected by western blot analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4286746&req=5

f3-bt-23-26: Atractylochromene inhibits β-catenin signaling pathway in SW-480 cells. SW-480 cells were treated with 20 μg/ml of atractylochromene for the indicated time, and cells were harvested to prepare nuclear and cytosolic fractions (A), and whole cell lysates (B). Relative expression levels of target proteins were detected by western blot analysis.
Mentions: To further confirm the inhibitory effect of AC on Wnt/β-catenin signaling pathway, β-catenin constitutively activated SW-480 colon cancer cell line were used. Treatment of AC (20 μg/ml) decreased the nuclear level of β-catenin in SW-480 cells in a time-dependent manner. But the levels of β-catenin in cytosol and whole cell lysate were not affected by AC (Fig. 3A and 3B). And a target gene of β-catenin, cyclin D1 was decreased by treatment of AC in SW-480 cells. The level of galectin-3, one of the β-catenin nuclear translocation modulators, was also decreased in nuclear of AC-treated SW-480 cells, but not in cytosolic fraction and whole cell lysates (Fig. 3A, B). These data indicate that AC inhibits Wnt/β-catenin signaling pathway through modulating the nuclear translocation of β-catenin and galectin-3 in colon cancer cells.

Bottom Line: The active compound was purified by activity-guided purification and the structure was identified as 2,8-dimethyl-6-hydroxy-2-(4-methyl-3-pentenyl)-2H-chromene (atractylochromene, AC).Furthermore, AC inhibits proliferation of colon cancer cell.Taken together, AC from A. macrocephala might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul 140-742.

ABSTRACT
Wnt/β-catenin signaling pathway was mutated in about 90% of the sporadic and hereditary colorectal cancers. The abnormally activated β-catenin increases the cancer cell proliferation, differentiation and metastasis through increasing the expression of its oncogenic target genes. In this study, we identified an inhibitor of β-catenin dependent Wnt pathway from rhizomes of Atractylodes macrocephala Koidzumi (Compositae). The active compound was purified by activity-guided purification and the structure was identified as 2,8-dimethyl-6-hydroxy-2-(4-methyl-3-pentenyl)-2H-chromene (atractylochromene, AC). AC suppressed β-catenin/T-cell factor transcriptional activity of HEK-293 reporter cells when they were stimulated by Wnt3a or inhibitor of glycogen synthase kinase-3β. AC down-regulated the nuclear level of β-catenin through the suppression of galectin-3 mediated nuclear translocation of β-catenin in SW-480 colon cancer cells. Furthermore, AC inhibits proliferation of colon cancer cell. Taken together, AC from A. macrocephala might be a potential chemotherapeutic agent for the prevention and treatment of human colon cancer.

No MeSH data available.


Related in: MedlinePlus