TRPV2 activation induces apoptotic cell death in human T24 bladder cancer cells: a potential therapeutic target for bladder cancer.
OBJECTIVE
To investigate the functional expression of the transient receptor potential vanilloid 2 (TRPV2) channel protein in human urothelial carcinoma (UC) cells and to determine whether calcium influx into UC cells through TRPV2 is involved in apoptotic cell death.


METHODS
The expression of TRPV2 mRNA in bladder cancer cell lines (T24, a poorly differentiated UC cell line and RT4, a well-differentiated UC cell line) was analyzed using reverse transcriptase-polymerase chain reaction. The calcium permeability of TRPV2 channels in T24 cells was investigated using a calcium imaging assay that used cannabidiol (CBD), a relatively selective TRPV2 agonist, and ruthenium red (RuR), a nonselective TRPV channel antagonist. The death of T24 or RT4 cells in the presence of CBD was evaluated using a cellular viability assay. Apoptosis of T24 cells caused by CBD was confirmed using an annexin-V assay and small interfering RNA (siRNA) silencing of TRPV2.


RESULTS
TRPV2 mRNA was abundantly expressed in T24 cells. The expression level in UC cells was correlated with high-grade disease. The administration of CBD increased intracellular calcium concentrations in T24 cells. In addition, the viability of T24 cells progressively decreased with increasing concentrations of CBD, whereas RT4 cells were mostly unaffected. Cell death occurred via apoptosis caused by continuous influx of calcium through TRPV2.


CONCLUSIONS
TRPV2 channels in UC cells are calcium-permeable and the regulation of calcium influx through these channels leads directly to the death of UC cells. TRPV2 channels in UC cells may be a potential new therapeutic target, especially in higher-grade UC cells.
Yamada
Takahiro
T
Department of Neurobiology and Anatomy, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
Ueda
Takashi
T
Shibata
Yasuhiro
Y
Ikegami
Yosuke
Y
Saito
Masaki
M
Ishida
Yusuke
Y
Ugawa
Shinya
S
Kohri
Kenjiro
K
Shimada
Shoichi
S
D017209:Apoptosis; D002295:Carcinoma, Transitional Cell / Q000473:pathology*; D006801:Humans; D050916:TRPV Cation Channels / Q000502:physiology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D050916:TRPV Cation Channels; C400769:TRPV2 protein, human