title: c-Fos is involved in inhibition of human bladder carcinoma T24 cells by brazilin.
abstract: Crude brazilin extract from Sappan wood has demonstrated strong anti tumor activity in the mouse model of human bladder carcinoma and clinical trial for intravesical therapy. Purified brazilin was confirmed the most active molecule in inhibition of bladder carcinoma T24 cells. Brazilin decreased proliferation and viability of T24 cells in a dose- and time-dependent manner, with a calculated LC50 of 32 µg/mL. More than 1,000 of genes were found upregulated and down regulated by brazilin treatment in digital gene expression profiling. Gene ontology analysis indicated that stress response, apoptosis, and cell cycle regulatory pathways were highly enriched. Among the regulated genes, c-Fos was the most and specifically upregulated. Overexpression of c-Fos in T24 cells resulted in tumor cell specific changes in cell morphology and viability. Over expression of stress-responsive gene, HSP70, and other highly upregulated genes did not have any effect on cell growth. Brazilin may inhibit T24 cell growth and trigger cell death through a c-Fos-mediated and tumor cell specific signaling pathway. Further studies of its down stream mediators may help to identify better tumor cell type specific drug targets.
authors: Research Institute of Applied Biology, Shanxi University, Taiyuan, Shanxi, China.
authors: Tingting
authors: T
authors: Zhang
authors: Xinping
authors: X
authors: Fan
authors: Lili
authors: L
authors: Song
authors: Lu
authors: L
authors: Ren
authors: Enbo
authors: E
authors: Ma
authors: Shengwan
authors: S
authors: Zhang
authors: Liansheng
authors: L
authors: Ren
authors: Yaowu
authors: Y
authors: Zheng
authors: Jianzhen
authors: J
authors: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001578:Benzopyrans / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016762:Genes, fos; D006801:Humans; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D001578:Benzopyrans; C044362:brazilin
keywords: brazilin; c-Fos; cell death; digital gene expression; gene ontology; human bladder carcinoma T24 cells; tumor cell inhibition