Dehydroglyasperin D Inhibits the Proliferation of HT-29 Human Colorectal Cancer Cells Through Direct Interaction With Phosphatidylinositol 3-kinase
Journal of Cancer Prevention
;
: 26-31, 2016.
Article
in English
| WPRIM
| ID: wpr-89894
ABSTRACT
BACKGROUND:
Despite recent advances in therapy, colorectal cancer still has a grim prognosis. Although licorice has been used in East Asian traditional medicine, the molecular properties of its constituents including dehydroglyasperin D (DHGA-D) remain unknown. We sought to evaluate the inhibitory effect of DHGA-D on colorectal cancer cell proliferation and identify the primary signaling molecule targeted by DHGA-D.METHODS:
We evaluated anchorage-dependent and -independent cell growth in HT-29 human colorectal adenocarcinoma cells. The target protein of DHGA-D was identified by Western blot analysis with a specific antibody, and direct interaction between DHGA-D and the target protein was confirmed by kinase and pull-down assays. Cell cycle analysis by flow cytometry and further Western blot analysis was performed to identify the signaling pathway involved.RESULTS:
DHGA-D significantly suppressed anchorage-dependent and -independent HT-29 colorectal cancer cell proliferation. DHGA-D directly suppressed phosphatidylinositol 3-kinase (PI3K) activity and subsequent Akt phosphorylation and bound to the p110 subunit of PI3K. DHGA-D also significantly induced G1 cell cycle arrest, together with the suppression of glycogen synthase kinase 3β and retinoblastoma phosphorylation and cyclin D1 expression.CONCLUSIONS:
DHGA-D has potent anticancer activity and targets PI3K in human colorectal adenocarcinoma HT-29 cells. To our knowledge, this is the first report to detail the molecular basis of DHGA-D in suppressing colorectal cancer cell growth.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphatidylinositols
/
Phosphorylation
/
Phosphotransferases
/
Prognosis
/
Retinoblastoma
/
Colorectal Neoplasms
/
Adenocarcinoma
/
Cell Cycle
/
Blotting, Western
/
HT29 Cells
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Journal of Cancer Prevention
Year:
2016
Type:
Article
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