Menthol Induces Cell Death via the TRPM8 Channel in the Human Bladder Cancer Cell Line T24

Objective: Growing evidence has shown that menthol has potent anticancer activity in various human cancers via the transient receptor potential melastatin 8 (TRPM8)-dependent pathway or in a TRPM8-independent manner. However, its effect on bladder cancer remains obscure. In the present investigation, we examined the expression of TRPM8 and the role of menthol in cells of the human bladder cancer cell line T24. Methods: RT-PCR, Western blotting and immunocytochemistry were used to confirm the expression and location of TRPM8 in T24 cells. Results: TRPM8 was highly expressed in T24 cells and located in both the cell membrane and cytoplasm. With the use of small interfering RNA to silence the expression of TRPM8, we found that menthol could increase the concentration of intracellular calcium and decrease cell viability via the TRPM8 channel in T24 cells. We also found that menthol could induce cell death through TRPM8 in T24 cells, rather than cell cycle arrest or apoptosis. Moreover, the detection of mitochondrial membrane potential showed that menthol could induce mitochondrial membrane depolarization in T24 cells. Conclusions: In the present study, we demonstrated that menthol can induce mitochondrial membrane depolarization via the TRPM8 channel in cells of the human bladder cancer cell line T24, resulting in cell death. It would be helpful to explore the precise mechanism of action of menthol in bladder cancer with a view to its possible use as intravesical chemotherapy. Copyright (C) 2009 S. Karger AG, Basel