| BackgroundBladder cancer has become a major cause of morbidity,mortality,and health-related costs.It is one of the most common malignant tumors of the urinary system.In men,the incidence is four times higher than that in women.Due to the rising incidence of bladder cancer,it has received more attention and been recognized as an important public health issue worldwide.Capsaicin(N-)is a homovanillic acid derivative and the chief pungent principle found in hot red chili peppers derived from Capsicum fruit extracts.Capsaicin not only acts as a tumor promoter or co-carcinogen in some cancer models,but is also an inhibitor of growth and tumor formation in some cancers.Numerous studies have shown that capsaicin treatment induced growth arrest and apoptosis of bladder cancer,cells and inhibited tumor formation through various mechanisms.Capsaicin promoted metabolic activation and increased oxidative stress,which is partly due to excess generation of reactive oxygen species(ROS).Moderate levels of ROS induce growth arrest and apoptosis and play a central role in the epithelial to mesenchymal transition(EMT)progression.Nuclear factor erythroid 2 related factor 2(Nrf2)is involved in the regulation of the antioxidant defense system,induces cytoprotective protein production and maintains the balance of cellular redox and metabolism.ObjectiveThe aim of the current study was to investigate the effects of capsaicin on proliferation and metastasis(through invasion,migration and epithelial-mesenchymal transition)of human bladder cancer cells.To elucidate the direct effects of the nutritional compound capsaicin on contraction of nuclear factor(erythroid-derived 2)-related factor 2(Nrf2).MethodsWe cultured human bladder cancer cells(RT112 and 253J)to investigate the effects of capsaicin on proliferation and metastasis of human bladder cancer cells.Bladder cancer cell invasion,migration and epithelial-mesenchymal transition were analyzed using MTT assays,Transwell assay,Wound Healing assay and Western Blot after different treatments(0,100?mol/L,200?mol/L)at different time points(Oh,12h,24h).ResultsCapsaicin decreased the proliferation of human bladder cancer cell lines.Bladder cancer cell proliferation was analyzed using MTT assays after different treatments at different time points.Capsaicin treatment of 253J and RT112 cells reduced the number of viable cells in a dose-and time-dependent manner.Phase contrast images show the results of the cell proliferation analyses.The capsaicin-treated cells lost their cell-cell contacts.There is statistical difference in treatment and control groups.Capsaicin inhibits human bladder cancer cell migration and invasion.Clear inhibition of wound healing was observed with 100 ?mol/L and 200 ?mol/L capsaicin in 253J cells and RT112 cells.The transwell experiments following DMSO and capsaicin treatments shows that capsaicin significantly inhibited cell invasion in a dose-dependent manner.Compared to the control group,the treatment groups had a decrease of approximately 90%of the invading cells.There is statistical difference in treatment and control groups.To further examine the effect of capsaicin on EMT.E-cadherin and Vimentin,EMT markers,were evaluated by Western blot analyses showed that an increase in E-cadherin protein and loss of Vimentin protein expression.Western blot analyses also showed the down regulation of the protein expression of n-Nrf2 and increased expression of c-Nrf2 induced by capsaicin treatment in dose-and time-dependent manners..Conclusion1.Capsaicin blocks human bladder cancer cell proliferation,migration and invasion.2.Capsaicin induced E-cadherin expression and decreased Vimentin protein expression,which are associated with epithelial-mesenchymal transition.3.In addition,capsaicin suppressed the translocation of nuclear factor(erythroid-derived 2)-related factor 2(Nrf2),served as an anti-tumorigenic agent in bladder cancer.Nrf2 is a target of capsaicin in the treatment of bladder cancer. |
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