Kaempferol suppresses bladder cancer tumor growth by inhibiting cell proliferation and inducing apoptosis.
The effects of the flavonoid compound, kaempferol, which is an inhibitor of cancer cell proliferation and an inducer of cell apoptosis have been shown in various cancers, including lung, pancreatic, and ovarian, but its effect has never been studied in bladder cancer. Here, we investigated the effects of kaempferol on bladder cancer using multiple in vitro cell lines and in vivo mice studies. The MTT assay results on various bladder cancer cell lines showed that kaempferol enhanced bladder cancer cell cytotoxicity. In contrast, when analyzed by the flow cytometric analysis, DNA ladder experiment, and TUNEL assay, kaempferol significantly was shown to induce apoptosis and cell cycle arrest. These in vitro results were confirmed in in vivo mice studies using subcutaneous xenografted mouse models. Consistent with the in vitro results, we found that treating mice with kaempferol significant suppression in tumor growth compared to the control group mice. Tumor tissue staining results showed decreased expressions of the growth related markers, yet increased expressions in apoptosis markers in the kaempferol treated group mice tissues compared to the control group mice. In addition, our in vitro and in vivo data showed kaempferol can also inhibit bladder cancer invasion and metastasis. Further mechanism dissection studies showed that significant down-regulation of the c-Met/p38 signaling pathway is responsible for the kaempferol mediated cell proliferation inhibition. All these findings suggest kaempferol might be an effective and novel chemotherapeutic drug to apply for the future therapeutic agent to combat bladder cancer.
Department of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, PR, China.
Qiang
Q
Dang
Department of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, PR, China.
Wenbin
W
Song
School of Pharmaceutical and Life Sciences, Changzhou University, Changzhou, Jiangsu, PR, China.
Defeng
D
Xu
Department of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, PR, China.
Yanmin
Y
Ma
Department of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, PR, China.
Feng
F
Li
Department of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, PR, China.
Jin
J
Zeng
Department of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, PR, China.
Guodong
G
Zhu
Department of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, PR, China.
Xinyang
X
Wang
Department of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, PR, China.
Luke S
LS
Chang
Department of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, PR, China.
Dalin
D
He
Department of Urology, The First Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Xi'an, PR, China.
Lei
L
Li
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D044949:Kaempferols / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D044949:Kaempferols; C006552:kaempferol; D019859:Proto-Oncogene Proteins c-met; D048051:p38 Mitogen-Activated Protein Kinases
apoptosis; bladder cancer; c-met/p38; cell growth; kaempferol