benzofurans and Urinary-Bladder-Neoplasms

The hypoxia-inducible factor-1α (HIF-1α) plays a critical role in tumor angiogenesis. It has been reported that the acetone extract of Angelica sinensis (AE-AS) rich in phthalides is able to inhibit cancer cell proliferation. However, whether AE-AS reduces cancer angiogenesis remains unknown. In this study, we demonstrated that AE-AS significantly inhibited the angiogenesis in vitro and in vivo evidenced by attenuation of the tube formation in hypoxic human umbilical vascular endothelial cells (HUVECs), and the vasculature generation in Matrigel plug, the chicken chorioallantoic membrane, and tumors. Treatment with AE-AS markedly decreased the protein accumulation and transcriptional activity of HIF-1α, vascular endothelial growth factor (VEGF) expression/secretion, and VEGFR2 phosphorylation in hypoxic human bladder cancer (T24) cells and tumor tissues accompanied by a reduction of tumor growth. Notably, AE-AS-induced HIF-1α protein degradation may, at least partly, attribute to inhibition of WSB-1-dependent pVHL degradation. Moreover, VEGFR2-activated PI3K/AKT/mTOR signaling pathway in hypoxic T24 cells was greatly inhibited by AE-AS. Collectively, AE-AS may be a potential anticancer agent by attenuating cancer angiogenesis via suppression of WSB-1/pVHL/HIF-1α/VEGF/VEGFR2 cascade.

Topics: Angelica sinensis; Animals; Antineoplastic Agents, Phytogenic; Benzofurans; Cell Line, Tumor; Chick Embryo; Chorioallantoic Membrane; Female; Gene Expression Regulation, Neoplastic; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intracellular Signaling Peptides and Proteins; Mice; Mice, Nude; Neovascularization, Pathologic; Plant Extracts; Proteins; Signal Transduction; Urinary Bladder Neoplasms; Vascular Endothelial Growth Factor A; Von Hippel-Lindau Tumor Suppressor Protein; Xenograft Model Antitumor Assays

Topics: Aged; Benzofurans; Capillary Resistance; Edema; Humans; Male; Middle Aged; Mouth Neoplasms; Radiotherapy, High-Energy; Urinary Bladder Neoplasms

Topics: Aniline Compounds; Animals; Benzofurans; Biphenyl Compounds; Carcinogens; Carcinoma; Ectromelia; Female; Liver Neoplasms; Male; Mice; Neoplasms, Experimental; Papilloma; Paraffin; Urinary Bladder Neoplasms; Vaccination

Topics: Animals; Benzofurans; Ear Neoplasms; Female; Kidney Neoplasms; Male; Mammary Neoplasms, Experimental; Neoplasms, Experimental; Rats; Urinary Bladder Neoplasms