decursin and Neoplasms

Topics: Angelica; Angelica sinensis; Animals; Antineoplastic Agents, Phytogenic; Benzopyrans; Butyrates; Disease Models, Animal; Drugs, Chinese Herbal; Humans; Liquid-Liquid Extraction; Medicine, Korean Traditional; Neoplasms; Phytotherapy; Plant Extracts; Plant Roots; Plants, Medicinal; Pyranocoumarins; Rodentia

Glutaminolysis is a typical hallmark of malignant tumors across different cancers. Glutamate dehydrogenase (GDH, GLUD1) is one such enzyme involved in the conversion of glutamate to α-ketoglutarate. High levels of GDH are associated with numerous diseases and is also a prognostic marker for predicting metastasis in colorectal cancer. Therefore, inhibiting GDH can be a crucial therapeutic target. Here in this study, we performed molecular docking analysis of 8 different plants derived single compounds collected from pubChem database for screening and selected decursin (DN) and decursinol angelate (DA). We performed molecular dynamics simulation (MD), monitored the stability, interaction for protein and docked ligand at 50 ns, and evaluated the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) free energy calculation on the twoselected compounds along with a standard inhibitor epigallocatechin gallate (EGCG) as reference. The final results showed the formation of stable hydrogen bond interactions by DN and DA in the residues of R400 and Y386 at the ADP activation site of GDH, which was important for the selective inhibition of GDH activity. Additionally, the total binding energy of DN and DA were -115.5 kJ/mol and -106.2 kJ/mol, which was higher than the standard reference GDH inhibitor EGCG (-92.8 kJ/mol). Furthermore, biochemical analysis for GDH inhibition substantiated our computational results and established DN and DA as novel GDH inhibitor. The percentage of IC

Topics: Butyrates; Enzyme Assays; Glutamate Dehydrogenase; Humans; Molecular Docking Simulation; Neoplasms

We have reported that a 10-herbal traditional formula containing Korean Angelica gigas Nakai (AGN) exerts potent anti-cancer efficacy and identified decursin and decursinol angelate (DA) from AGN as novel anti-androgens. Here, we determined whether AGN would exert in vivo anti-cancer activity and whether decursin or DA could account for its efficacy. The AGN ethanol extract was tested against the growth of mouse Lewis lung cancer (LLC) allograft in syngenic mice or human PC-3 and DU145 prostate cancer xenograft in immunodeficient mice. The pharmacokinetics of decursin and DA were determined. The AGN extract significantly inhibited LLC allograft growth (30 mg/kg) and PC-3 and DU145 xenograft growth (100 mg/kg) without affecting the body weight of the host mice. Biomarker analyses revealed decreased cell proliferation (Ki67, PCNA), decreased angiogenesis (VEGF, microvessel density) and increased apoptosis (TUNEL, cPARP) in treated tumors. Decursin and DA injected intraperitoneally were rapidly hydrolyzed to decursinol. Decursinol and decursin at 50 mg/kg inhibited LLC allograft growth to the same extent, comparable to 30 mg AGN/kg. Therefore the AGN extract possessed significant in vivo anti-cancer activity, but decursin and DA only contributed moderately to that activity, most likely through decursinol.

Topics: Administration, Oral; Angelica; Angiogenesis Inhibitors; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Benzopyrans; Butyrates; Cell Line, Tumor; Cell Proliferation; Humans; Injections, Intraperitoneal; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms; Phytotherapy; Plant Extracts; Pyranocoumarins

The in vivo anti-tumor activities of decursinol angelate (1) and decursin (2) isolated from the roots of Angelica gigas were investigated. These two compounds, when administered consecutively for 9 days at 50 and 100 mg/kg i.p. in mice, caused a significant increase in the life span and a significant decrease in the tumor weight and volume of mice inoculated with Sarcoma-180 tumor cells. These results suggest that decursinol angelate (1) and decursin (2) from A. gigas have anti-tumor activities.

Topics: Angelica; Animals; Antineoplastic Agents, Phytogenic; Benzopyrans; Butyrates; Cell Line, Tumor; Fluorouracil; Injections, Intraperitoneal; Korea; Male; Medicine, East Asian Traditional; Mice; Mice, Inbred ICR; Neoplasm Transplantation; Neoplasms; Plant Extracts; Plant Roots; Sarcoma 180; Survival Rate