title: Curcumin potentiates antitumor activity of cisplatin in bladder cancer cell lines via ROS-mediated activation of ERK1/2.
abstract: Resistance of bladder cancer to cisplatin is a major obstacle to successful treatment. In the current study, we investigated the apoptotic effects of curcumin and cisplatin co-treatment in 253J-Bv(p53 wild-type) and T24(p53 mutant) bladder cancer. We found that curcumin and cisplatin co-treatment primarily targets reactive oxygen species(ROS) and extracellular regulated kinase(ERK) signaling during the apoptosis induction in bladder cancer. The apoptosis rate in 253J-Bv and T24 cells co-treated with curcumin and cisplatin was increased compared to that in cells exposed to single-agent treatment conditions. Also, caspase-3 activation and ROS production were observed in both cells treated with curcumin and cisplatin, together with upregulation of p-MEK and p-ERK1/2 signaling. NAC(ROS scavenger) and U0126(ERK inhibitor) inhibited apoptosis induced by curcumin and cisplatin. In addition, when 253J-Bv cells were co-treated with curcumin and cisplatin, p53 and p21 expression levels were markedly increased when compared to controls. Unlike 253J-Bv cells, T24 cells were co-treated with curcumin and cisplatin revealed an induction of apoptosis through decreased p-signal transducer and activator of transcription 3(STAT3) expression. Moreover, pretreatment with U0126 suppressed curcumin and cisplatin-induced upregulation of p53, p21, and p-STAT3 and downregulation of survival proteins in both cells. In conclusion, co-treatment with curcumin and cisplatin synergistically induced apoptosis through ROS-mediated activation of ERK1/2 in bladder cancer.
authors: Department of Urology, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Bong Hee
authors: BH
authors: Park
authors: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors: Joung Eun
authors: JE
authors: Lim
authors: Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Hwang Gyun
authors: HG
authors: Jeon
authors: Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Seong Il
authors: SI
authors: Seo
authors: Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Hyun Moo
authors: HM
authors: Lee
authors: Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Han Yong
authors: HY
authors: Choi
authors: Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Seong Soo
authors: SS
authors: Jeon
authors: Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: Byong Chang
authors: BC
authors: Jeong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis; D002070:Butadienes / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009570:Nitriles / Q000494:pharmacology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D003474:Curcumin; D002945:Cisplatin
keywords: ERK; bladder cancer; cisplatin; curcumin; oxidative stress