High-dose chemotherapeutics of intravesical chemotherapy rapidly induce mitochondrial dysfunction in bladder cancer-derived spheroids.
Bottom Line: Two hours after exposure to MMC, the mitochondrial membrane potential decreased and the mitochondria were fragmented, while plasma membrane integrity was maintained.ATP levels rapidly decreased in CTOS after exposure to EPI or MMC.In the CTOS prepared directly from 19 surgical specimens exposed to EPI and MMC, the decrease of ATP levels varied among patients.
Affiliation: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.Show MeSH
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Mentions: Mitochondrial dysfunction plays a pivotal role in mechanisms of cell death, including both apoptosis and necrosis.25,26 Therefore, we monitored mitochondrial membrane potential, Δψm, in CTOS before and after exposure to MMC using fluorescence microscopy and flow cytometric analysis. After 2 h exposure to MMC, Δψm in CTOS decreased remarkably (Fig.3a,b). Next, we investigated the morphology of mitochondria with a fluorescent probe that stains mitochondria independent of Δψm. Fluorescence microscopy revealed notable mitochondrial fragmentation after 2 h exposure to MMC (Fig.3c). Thus, mitochondrial function and morphology were severely impaired after 2 h exposure to high-dose MMC.
Affiliation: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan; Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.