Abstract
Human bladder cancer (BC) cells exhibit a high basal level of autophagic activity with accumulation of acridine-orange(AO)-stained acidic vesicular organelles. The rapid AO relocalization was observed in treated BC cells under blue-light emission. To investigate the cytotoxic effects of AO on human BC cell lines under blue-light exposure, human immortalized uroepithelial (SV-Huc-1) and BC cell lines (5637 and T24) were treated with indicated concentrations of AO or blue-light exposure alone and in combination. The cell viability was then determined using WST-1, time-lapse imaging with a Cytosmart System and continuous quantification with a multi-mode image-based reader. Treatment of AO or blue-light exposure alone did not cause a significant loss of viability in BC cells. However, AO exhibited a dose-dependent increment of cytotoxicity toward BC cells under blue-light exposure. Furthermore, the tumor formation of BC cells with treatment was significantly reduced when evaluated in a mouse xenograft model. The photodamage caused by AO was nearly neglected in SV-Huc-1 cells, suggesting a differential effect of this treatment between cancer and normal cells. In summary, AO, as a photosensitizer, disrupts acidic organelles and induces cancer cell death in BC cells under blue-light irradiation. Our findings may serve as a novel therapeutic strategy against human BC.
Highlights
Bladder cancer (BC) remains a commonly diagnosed urological malignancy with a high recurrence rate
Acridine orange (AO) vital staining could not reflect the autophagic status in human bladder cancer cells, we detected autophagy induction by cisplatin in prostate and bladder cancer cells
These results suggested that AO vital staining as an indication for detecting autophagy induction is not adequate in bladder cancer (BC) cells
Summary
Bladder cancer (BC) remains a commonly diagnosed urological malignancy with a high recurrence rate. Under AO staining, the cytoplasm and nucleoli fluoresce green, whereas the acidic compartments, such as lysosomes or autophagolysosomes, fluoresce bright-red or orange-red with blue-light excitation[6]. We failed to detect autophagy when using AO as a vital staining dye in human BC cells in a previous study[7]. The red dots representing AVOs were sometimes missing and the intensity of red fluorescence was not increased in AO-stained BC cells, despite the confirmation of the existence of autophagy[7]. Decreased cell viability was observed in AO-stained BC cells This observation suggested that AO may exhibit cytotoxicity toward human bladder cancer cells even when treated with the regular dose that is commonly used to detect autophagy www.nature.com/scientificreports/. It is possible that cellular damage occurred in AO-stained BC cells during the detection processes with blue-light exposure. We aimed to present the AO-mediated photodamage on human BC cells compared with human immortalized uroepithelial cells (SV-Huc[1])
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