Dehydroglyasperin D Inhibits the Proliferation of HT-29 Human Colorectal Cancer Cells Through Direct Interaction With Phosphatidylinositol 3-kinase.
10.15430/JCP.2016.21.1.26
- Author:
Sung Keun JUNG
1
;
Chul Ho JEONG
Author Information
1. Research Group of Nutraceuticals for Metabolic Syndrome, Korea Food Research Institute, Seongnam, Keimyung University, Daegu, Korea.
- Publication Type:Original Article
- Keywords:
PI3K;
Dehydroglyasperin D;
Colorectal neoplasms;
Proliferation;
Cell cycle
- MeSH:
Adenocarcinoma;
Blotting, Western;
Cell Cycle;
Cell Proliferation;
Colorectal Neoplasms*;
Cyclin D1;
Flow Cytometry;
G1 Phase Cell Cycle Checkpoints;
Glycogen Synthase Kinases;
Glycyrrhiza;
HT29 Cells;
Humans*;
Medicine, East Asian Traditional;
Phosphatidylinositol 3-Kinase*;
Phosphatidylinositols*;
Phosphorylation;
Phosphotransferases;
Prognosis;
Retinoblastoma
- From:Journal of Cancer Prevention
2016;21(1):26-31
- CountryRepublic of Korea
- Language:English
-
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.
