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

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.

Antioxidant activities of licorice-derived prenylflavonoids

Glycyrrhiza uralensis (or licorice) is a widely used Oriental herbal medicine from which the phenylflavonoids dehydroglyasperin C (DGC), dehydroglyasperin D (DGD), and isoangustone A (IsoA) are derived. The purpose of the present study was to evaluate the antioxidant properties of DGC, DGD, and IsoA. The three compounds showed strong ferric reducing activities and effectively scavenged DPPH, ABTS+, and singlet oxygen radicals. Among the three compounds tested, DGC showed the highest free radical scavenging capacity in human hepatoma HepG2 cells as assessed by oxidant-sensitive fluorescent dyes dichlorofluorescein diacetate and dihydroethidium bromide. In addition, all three compounds effectively suppressed lipid peroxidation in rat tissues as well as H2O2-induced ROS production in hepatoma cells. This study demonstrates that among the three phenylflavonoids isolated from licorice, DGC possesses the most potent antioxidant activity, suggesting it has protective effects against chronic diseases caused by reactive oxygen species as well as potential as an antioxidant food additive.