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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 TOPFlash activity. After treatment of Wnt3a CM (A) or LiCl (20 mM) (B), and atractylochromene (20 μg/ml) to the TOPFlash reporter stable HEK-293 cells for 15 h, TOPFlash reporter activity was determined by measuring firefly luciferase activity. Data shows the relative luciferase activity by mean ± S.D. of three experiments. The asterisks indicate a significant difference from the Wnt3a CM treated vehicle group (*p<0.01).
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f2-bt-23-26: Atractylochromene inhibits TOPFlash activity. After treatment of Wnt3a CM (A) or LiCl (20 mM) (B), and atractylochromene (20 μg/ml) to the TOPFlash reporter stable HEK-293 cells for 15 h, TOPFlash reporter activity was determined by measuring firefly luciferase activity. Data shows the relative luciferase activity by mean ± S.D. of three experiments. The asterisks indicate a significant difference from the Wnt3a CM treated vehicle group (*p<0.01).

Mentions: As shown in Fig. 2A, treatment of AC inhibits TOPflash activity in Wnt3a CM-treated stable reporter HEK-293 cells in a dose-dependent manner. The activity of FOPFlash, a negative control reporter with mutated β-catenin/TCF binding elements, was not altered by the treatment of AC and Wnt3a CM (data not shown). To test whether the GSK-3β was involved in the inhibition of β-catenin response transcription, we treated HEK cells with LiCl as an inhibitor of GSK-3β. AC treatment also inhibits TOPflash activity in LiCl-treated HEK-293 cells (Fig. 2B).


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 TOPFlash activity. After treatment of Wnt3a CM (A) or LiCl (20 mM) (B), and atractylochromene (20 μg/ml) to the TOPFlash reporter stable HEK-293 cells for 15 h, TOPFlash reporter activity was determined by measuring firefly luciferase activity. Data shows the relative luciferase activity by mean ± S.D. of three experiments. The asterisks indicate a significant difference from the Wnt3a CM treated vehicle group (*p<0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-bt-23-26: Atractylochromene inhibits TOPFlash activity. After treatment of Wnt3a CM (A) or LiCl (20 mM) (B), and atractylochromene (20 μg/ml) to the TOPFlash reporter stable HEK-293 cells for 15 h, TOPFlash reporter activity was determined by measuring firefly luciferase activity. Data shows the relative luciferase activity by mean ± S.D. of three experiments. The asterisks indicate a significant difference from the Wnt3a CM treated vehicle group (*p<0.01).
Mentions: As shown in Fig. 2A, treatment of AC inhibits TOPflash activity in Wnt3a CM-treated stable reporter HEK-293 cells in a dose-dependent manner. The activity of FOPFlash, a negative control reporter with mutated β-catenin/TCF binding elements, was not altered by the treatment of AC and Wnt3a CM (data not shown). To test whether the GSK-3β was involved in the inhibition of β-catenin response transcription, we treated HEK cells with LiCl as an inhibitor of GSK-3β. AC treatment also inhibits TOPflash activity in LiCl-treated HEK-293 cells (Fig. 2B).

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