Isoangustone A present in hexane/ethanol extract of Glycyrrhiza uralensis induces apoptosis in DU145 human prostate cancer cells via the activation of DR4 and intrinsic apoptosis pathway.

Abstract

Glycyrrhiza uralensis (licorice) is one of the most frequently prescribed ingredients in Oriental medicine, and licorice extract has been shown to exert anti-carcinogenic effects. However, its use as a cancer chemopreventive agent is rather limited, due to the fact that its principal component, glycyrrhizin, is known to induce hypertension. This study determined the effects of a hexane/ethanol extract of G. uralensis (HEGU), which contains undetectable amounts of glycyrrhizin, on the apoptosis of androgen-insensitive DU145 cells. HEGU induced apoptosis and increased the levels of cleaved caspase-9, caspase-7, caspase-3 and poly (ADP-ribose) polymerase (PARP). HEGU also induced mitochondrial membrane depolarization and cytochrome c release to the cytosol. HEGU increased the levels of Fas, death receptor 4 (DR4), cleaved caspase-8, Mcl-1S, and truncated Bid proteins. A caspase-8 inhibitor suppressed HEGU-induced apoptosis. An active fraction of HEGU was separated via column chromatography and the structure of the active compound isoangustone A was identified via 1H-NMR and 13C-NMR. Isoangustone A increased apoptotic cells, the cleavage of PARP and caspases, and the levels of DR4 and Mcl-1S. Transfection with DR4 small interfering RNA attenuated HEGU- and isoangustone A-induced apoptosis. These results demonstrate that the activation of DR4 contributes to HEGU- and isoangustone A-induced apoptosis of DU145 cells.

• Authors: Mi Ra Seon, Soon Sung Lim, Hyun Ju Choi, So Young Park, Han Jin Cho, Jin-Kyu Kim, Jongdai Kim, Dae Young Kwon, Jung Han Yoon Park
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 54 Issue 9 Pg. 1329-39 (Sep 2010) ISSN: 1613-4133 [Electronic] Germany
• PMID: 20229524 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Caspase Inhibitors
• Isoflavones
• Myeloid Cell Leukemia Sequence 1 Protein
• Plant Extracts
• Proto-Oncogene Proteins c-bcl-2
• RNA, Small Interfering
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• TNFRSF10A protein, human
• isoangustone A
• Poly(ADP-ribose) Polymerases
• Caspases

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Caspase Inhibitors
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Glycyrrhiza uralensis (chemistry)
• Humans
• Isoflavones (chemistry, isolation & purification, pharmacology)
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, enzymology)
• Molecular Structure
• Myeloid Cell Leukemia Sequence 1 Protein
• Permeability (drug effects)
• Plant Extracts (chemistry, pharmacology)
• Poly(ADP-ribose) Polymerases (metabolism)
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• RNA, Small Interfering
• Receptors, TNF-Related Apoptosis-Inducing Ligand (genetics, metabolism)
• Signal Transduction (drug effects)