Reduction in mitochondrial oxidative stress mediates hypoxia-induced resistance to cisplatin in human transitional cell carcinoma cells

• DOI: 10.1016/j.neo.2021.05.013
• Publication Date: 2021-06-13T21:30:18Z
• Authors: Myung-Chul Kim; Sung-Hyun Hwang; Yeseul Yang; Na-Yon Kim; Yongbaek Kim
• Keywords: Hypoxia; Mitochondrial ROS

Tumor hypoxia is known to promote the acquisition of more aggressive phenotypes in human transitional cell carcinoma (TCC), including drug resistance. Accumulating evidence suggests that mitochondria play a central role chemoresistance TCC. However, hypoxia-induced resistance TCC remains elusive. The present study investigated function using line under hypoxic conditions. In vitro (0.1% O2, 48 h) was achieved by incubating cells air chamber. Mitochondrial events involving were assessed. Hypoxia significantly reduced cisplatin-induced apoptosis cells. Additionally, substantially decreased level mitochondrial reactive oxygen species (ROS) generated cisplatin treatment. Analogously, elimination ROS rescued from apoptosis. enhanced hyperpolarization, which not related ATP production or reversal synthase activity. DNA (mtDNA) amplification efficiency data illustrated prevented oxidative damage mitogenome. Moreover, transmission electron microscopy revealed disruption ultrastructure abated Notably, depletion mtDNA ethidium bromide abrogated cisplatin. Taken together, demonstrated exposed conditions rendered less sensitive stress induced treatment, leading