Characterization of mitochondria in cisplatin-resistant human ovarian carcinoma cells

Abstract

Treatment of these cells with cisplatin or hydrogen peroxide induces complete mitochondrial DNA damage in OV 2008 cells, while only partial DNA-destruction is observed in C13 cells, strongly suggesting that mitochondria are resistant to cisplatin and oxidative stress response. Continuous oxygen consumption of these cells monitored by a multi-channel dissolved oxygen meter is 1.70-fold higher in OV 2008 cells than C13 cells and the oxygen consumption was decreased by 30% in C13 cells, suggesting mitochondrial respiratory malfunction in these cells. The hypothesis generated here is that mitochondrial DNA resistance to cisplatin and oxidative stress response might be one of the main characteristics concerning the lower level of apoptosis induced by cisplatin. However, the mechanism by which the mitochondrial DNA encoded molecule is involved in cisplatin resistance remains to be determined.

Human mitochondrial Mrs2 protein promotes multidrug resistance in gastric cancer cells by regulating p27, cyclin D1 expression and cytochrome C release

“…1 The connection between mitochondrial activity and cellular response to chemotherapeutic agents was previously demonstrated. [19][20][21] Compared with drugsensitive cells, cells of MDR had different mitochondrial activity, such as lower mitochondrial membrane potential, smaller transmission of protons against the proton gradient, lower levels of reactive oxygen when stressed, etc. 22 Mrs2p is the only identified protein which transporting Mg in mitochondria of mammals.…”

Targeting Mitochondrial DNA with a Platinum-Based Anticancer Agent

“…Mitochondria also appear to play a role in mediating cellular resistance to cisplatin. Cisplatin-resistant cell lines have elevated mitochondrial membrane potentials (Andrews et al, 1992; Isonishi et al, 2001), sustain less damage to mtDNA when treated with the drug (Hirama et al, 2006), and exhibit substantially less mitochondrial uptake of cisplatin (Groessl et al, 2011) compared to non-resistant parent lines.…”

Hyper-phosphorylation of Sequestosome-1 Distinguishes Resistance to Cisplatin in Patient Derived High Grade Serous Ovarian Cancer Cells

“…For example, cisplatin was shown to preferentially bind to mitochondrial DNA in head and neck squamous cells (53) and to induce mitochondrial-dependent reactive oxygen species (ROS) response in Saccharomyces cerevisiae (54), contributing to the cytotoxic effect caused by DNA damage. Recent interest has developed in the role of "metabolic reprogramming" in development of ovarian cancer resistance by studying the mitochondrial function and metabolism in the presence of cisplatin (55)(56)(57)(58), but a detailed discussion is beyond the scope of our findings.…”