title: Antiangiogenesis as the novel mechanism for justicidin A in the anticancer effect on human bladder cancer.
abstract: Justicidin A (JA) is one of the methanol extracts of Justicia procumbens and was reported to induce apoptosis and inhibit the proliferation of human colon cancer cells. Using bladder cancer as a paradigm, this study was designed to identify the novel molecular basis underlying the antiangiogenic activities of JA and its potential in cancer therapy. Human bladder cancer cell lines (TSGH8301 and RT4) and immortalized uroepithelial cell lines (E6 and E7) were chosen to investigate the efficacy of JA in cell proliferation, apoptosis, and angiogenesis in vitro. The biological effects of JA treatment in vivo were examined using a xenograft tumor model in SCID mice. JA showed a dose-dependent and time-dependent inhibition of cell proliferation on TSGH8301 cancer cells, with IC50 values determined to be 0.44 μmol/l. Of interest, TSGH8301 cancer cells were more sensitive to JA than E7 immortalized uroepithelial cells, especially at lower concentrations. We further showed that JA inhibited the autocrine production of angiogenic factors and matrix-degrading enzymes in vitro and microvessel density in SCID mice in vivo (P< 0.01). Both differential cytotoxicity and angiogenesis inhibition of JA were confirmed by SCID mice experiments. Together, JA showed antiangiogenesis in vitro and in vivo through pleiotropic positive and negative regulators of angiogenesis molecules. The current investigation supports the potential of JA as an alternative chemoprevention agent for human bladder cancer.
authors.affiliation: aThe Institute of Basic Medical Sciences bDepartment of Parasitology cDepartment of Microbiology and Immunology dDepartment of Urology, College of Medicine, National Cheng Kung University eDepartment of Pathology, National Cheng Kung University Hospital, Tainan fDepartment of Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Wang
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Chuang
authors.forename: Tsuey-Yu
authors.initials: TY
authors.lastname: Chang
authors.forename: Shen-Jeu
authors.initials: SJ
authors.lastname: Won
authors.forename: Hung-Wen
authors.initials: HW
authors.lastname: Tsai
authors.forename: Chung-Ta
authors.initials: CT
authors.lastname: Lee
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Cheng
authors.forename: Tzong-Shin
authors.initials: TS
authors.lastname: Tzai
authors.forename: Hsiao-Sheng
authors.initials: HS
authors.lastname: Liu
authors.forename: Nan-Haw
authors.initials: NH
authors.lastname: Chow
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004148:Dioxolanes / Q000494:pharmacology* / Q000627:therapeutic use; D064593:Heterografts; D006801:Humans; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D004148:Dioxolanes; D017705:Lignans; C049719:justicidins