J Cancer Prev.  2016 Mar;21(1):26-31. 10.15430/JCP.2016.21.1.26.

Dehydroglyasperin D Inhibits the Proliferation of HT-29 Human Colorectal Cancer Cells Through Direct Interaction With Phosphatidylinositol 3-kinase

• Jung SK
• Jeong CH

• KMID: 2161520
• DOI: http://doi.org/10.15430/JCP.2016.21.1.26

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.

Keyword

PI3K; Dehydroglyasperin D; Colorectal neoplasms; Proliferation; Cell cycle

MeSH Terms

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
Cyclin D1
Glycogen Synthase Kinases
Phosphatidylinositol 3-Kinase
Phosphatidylinositols
Phosphotransferases