title: Naringenin inhibits migration of bladder cancer cells through downregulation of AKT and MMP‑2.
abstract: Bladder cancer is one of the causes of cancer‑related death and has a high mortality rate due to its metastatic ability. Naringenin, a bioactive compound predominantly found in citrus fruits, exhibits several cellular functions, including anti‑oxidant, ‑lipidemia and ‑cancer abilities. However, the effects of naringenin on bladder cancer cells are yet to be elucidated. The present study investigated the molecular mechanisms underlying the effects of naringenin on the migration of TSGH‑8301 bladder cancer cells. Treatment with naringenin at doses ranging between 0 and 300 µM over a period of 24 h was found to reduce cell viability. Furthermore, zymography and western blot analysis revealed that naringenin reduced the expression of matrix metalloproteinase (MMP)‑2 in a dose‑dependent manner, and repressed its activity. Naringenin also reduced TSGH‑8301 cell migration in a concentration‑dependent manner, as evidenced by wound healing and Transwell® assays. In addition, naringenin was found to inhibit AKT activity and block the nuclear translocation of nuclear factor κ‑light‑chain‑enhancer of activated B cells. In conclusion, the findings of the present study show that naringenin is capable of inhibiting bladder cancer cell migration through the downregulation of the AKT and MMP‑2 pathways.
authors.affiliation: Division of Urology, Department of Surgery, Chi‑Mei Foundation Medical Center, Tainan, Taiwan, R.O.C.
authors.forename: Alex Chien Hwa
authors.initials: AC
authors.lastname: Liao
authors.affiliation: Department of Urology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, R.O.C.
authors.forename: Chia-Cheng
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Yei-Chung
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Chi-Wei
authors.initials: CW
authors.lastname: Yeh
authors.affiliation: Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: You-Cheng
authors.initials: YC
authors.lastname: Hseu
authors.affiliation: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Jer-Yuh
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Li-Sung
authors.initials: LS
authors.lastname: Hsu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D001749:Urinary Bladder Neoplasms / Q000378:metabolism
chemical_list: D044950:Flavanones; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C005273:naringenin