ABSTRACT
Cat's whiskers (Orthosiphon stamineus) is commonly used as Java tea to treat kidney stones including a variety of angiogenesis-dependent diseases such as tumorous edema, rheumatism, diabetic blindness, and obesity. In the present study, antitumor potential of standardized 50% ethanol extract of O. stamineus leaves (EOS) was evaluated against colorectal tumor in athymic mice and antiangiogenic efficacy of EOS was investigated in human umbilical vein endothelial cells (HUVEC). EOS at 100 mg/kg caused 47.62 ± 6.4% suppression in tumor growth, while at 200 mg/kg it caused 83.39 ± 4.1% tumor regression. Tumor histology revealed significant reduction in extent of vascularization. Enzyme-linked immunosorbent assay showed EOS (200 mg/kg) significantly reduced the vascular endothelial growth factor (VEGF) level in vitro (211 ± 0.26 pg/ml cell lysate) as well as in vivo (90.9 ± 2 pg/g tissue homogenate) when compared to the control (378 ± 5 and 135.5 ± 4 pg, respectively). However, EOS was found to be noncytotoxic to colon cancer and endothelial cells. In vitro, EOS significantly inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs). EOS suppressed VEGF-induced phosphorylation of VEGF receptor-2 in HUVECs. High performance liquid chromatography (HPLC) analysis of EOS showed high rosmarinic acid contents, whereas phytochemical analysis revealed high protein and phenolic contents. These results demonstrated that the antitumor activity of EOS may be due to its VEGF-targeted antiangiogenicity.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Colonic Neoplasms/drug therapy , Orthosiphon/chemistry , Plant Extracts/pharmacology , Animals , Cell Movement/drug effects , Cell Proliferation/drug effects , Chromatography, High Pressure Liquid , Colonic Neoplasms/blood supply , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Drug Screening Assays, Antitumor , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Mice , Mice, Nude , Phosphorylation , Plant Extracts/chemistry , Plants, Medicinal , Tyrosine/metabolism , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism , Xenograft Model Antitumor AssaysABSTRACT
The asymmetric unit of the title compound, C(30)H(46)O(4)·0.5CHCl(3), consists of one koetjapic acid [systematic name: (3R,4aR,4bS,7S,8S,10bS,12aS)-7-(2-carboxy-ethyl)-3,4b,7,10b,12a-penta-methyl-8-(prop-1-en-2-yl)-1,2,3,4,4a,4b,5,6,7,8,9,10,10b,11,12,12a-hexa-deca-hydro-chrysene-3-carboxylic acid] mol-ecule and one half-mol-ecule of chloro-form solvent, which is disordered about a twofold rotation axis. The symmetry-independent component is further disordered over two sites, with occupancies of 0.30 and 0.20. The koetjapic acid contains a fused four-ring system, A/B/C/D. The A/B, B/C and C/D junctions adopt E/trans/cis configurations, respectively. The conformation of ring A is inter-mediate between envelope and half-chair and ring B adopts an envelope conformation whereas rings C and D adopt chair conformations. A weak intra-molecular C-Hâ¯O hydrogen bond is observed. The koetjapic acid mol-ecules are linked into dimers by two pairs of inter-molecular O-Hâ¯O hydrogen bonds. The dimers are stacked along the c axis.
