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Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label instillation therapy into the bladder. To reduce potential side effects, continuous efforts are made to optimise the therapeutic potential of drugs, thereby reducing the effective dose and consequently the pharmacological burden of the medication. We recently demonstrated that it is possible to significantly increase the therapeutic efficacy of mitomycin C against a bladder carcinoma cell line by exposure to non-toxic doses of blue light (453 nm). In the present study, we investigated whether the therapeutically supportive effect of blue light can be further enhanced by the additional use of the wavelength-specific photosensitiser riboflavin. We found that the gemcitabine-induced cytotoxicity of bladder cancer cell lines (BFTC-905, SW-1710, RT-112) was significantly enhanced by non-toxic doses of blue light in the presence of riboflavin. Enhanced cytotoxicity correlated with decreased levels of mitochondrial ATP synthesis and increased lipid peroxidation was most likely the result of increased oxidative stress. Due to these properties, blue light in combination with riboflavin could represent an effective therapy option with few side effects and increase the success of local treatment of bladder cancer, whereby the dose of the chemotherapeutic agent used and thus the chemical load could be significantly reduced with similar or improved therapeutic success. [ABSTRACT FROM AUTHOR]

Human urothelial bladder carcinoma (uBC) is the second most tumor entity of the urogenital tract. As far as possible, therapy for non-muscle invasive uBC takes place as resection of the tumor tissue, followed by intravesical chemotherapy or immunotherapy. Because of the high recurrence rate of uBC, there is a need for improved efficiency in the treatment. In the present in vitro study we have evaluated a new approach to enhance the cytotoxic efficiency of Mitomycin C (MMC), which is commonly used for intravesical treatment of uBC on the relevant urothelial cancer cell line RT112. For that we used quasi-monochromatic blue light (453 ± 10 nm) at its non-toxic dose of 110 J/cm2 as an additive stimulus to enhance the therapeutic efficiency of MMC (10 μg/ml). We found, that blue light exposure of RT112 cells led to a very strong increase in intracellular production of reactive oxygen species (ROS) and to a significant reduction (p < 0.05) of all function parameters of mitochondrial respiration, including basal activity and ATP production. Although not being toxic when used as a single impact, together with MMC blue light strongly enhanced the therapeutic efficiency of MMC in the form of significantly enhanced cytotoxicity via apoptosis and secondary necrosis. Our results clearly show that blue light, most likely due to its ability to increase intracellular ROS production and reduce mitochondrial respiration, increased the cytotoxic efficiency of MMC and therefore might represent an effective, low-side-effect, and success-enhancing therapy option in the local treatment of bladder cancer. • Blue light enhances ROS production in human urothelial bladder carcinoma cells. • Blue light reduces mitochondrial respiration and ATP production in these tumor cells. • Both properties of Blue light enhance the cytotoxic efficiency of Mitomycin C. [ABSTRACT FROM AUTHOR]