title: Curcumin-induced heme oxygenase-1 expression plays a negative role for its anti-cancer effect in bladder cancers.
abstract: Some phytochemicals with the characteristics of cytotoxicity and anti-metastasis has generated intense interest among the invasive cancer study. Curcumin, one of these anti-cancer phytochemicals, has been reported to induce the cytoprotective enzyme heme oxygenase-1 expression. Since heme oxygenase-1 has been suggested to enhance cancer cell invasion, we investigated the anti-invasive effect of curcumin when heme oxygenase-1 was knocked down in vitro, and the heme oxygenase-1 expression after curcumin treatment in vivo. Curcumin inhibited cell viability and the MMP-2/9 activities of human bladder cancer cells. At 10 μM, curcumin inhibited cell viability and cell invasive activity by 15% and 40%, respectively. Ten micrometer curcumin increased the intracellular reactive oxygen species concentration and heme oxygenase-1 protein and mRNA expression in bladder cancer cells. The anti-invasive activity of curcumin was elevated when heme oxygenase-1 was knocked down by siRNA or inhibited by pharmacological inhibitor. In vivo, curcumin induced heme oxygenase-1 protein expression in the lung tissue of murine lung metastasis tumor model and in the bladder tissue of murine orthotopic bladder tumor model. Taken together, our data suggest that curcumin-induced heme oxygenase-1 attenuates the anti-invasive effect of curcumin in cancer therapy, and co-treatment by heme oxygenase-1 inhibitor enhances the anti-invasive activity of curcumin.
authors: Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors: Szu-Yuan
authors: SY
authors: Wu
authors: Ying-Ray
authors: YR
authors: Lee
authors: Chin-Chin
authors: CC
authors: Huang
authors: Yi-Zhen
authors: YZ
authors: Li
authors: Yi-Sheng
authors: YS
authors: Chang
authors: Chu-Yi
authors: CY
authors: Yang
authors: Jiann-Der
authors: JD
authors: Wu
authors: Yi-Wen
authors: YW
authors: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D017382:Reactive Oxygen Species; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; D003474:Curcumin