Wilson disease ATPase (ATP7B) has been implicated in the resistance of cancer cells to cisplatin. Using a simple in vivo assay in bacterial culture, in the present study we demonstrate that ATP7B can confer resistance to cisplatin by sequestering the drug in its N-terminal metal-binding domain without active drug extrusion from the cell. Expression of a protein fragment containing four N-termin...

KCP-4 is a cisplatin-resistant cell line established from human epidermoid carcinoma KB-3-1 cells. Although our previous study revealed that one of the mechanisms for cisplatin resistance in KCP-4 cells is the activation of NF-κB, its high resistance is considered to be induced by multiple mechanisms. In the present study, we explored other factors involved in the development of cisplatin resis...

Dictyostelium discoideum is a useful model for studying mechanisms of cisplatin drug sensitivity. Our previous findings, that mutations in sphingolipid metabolism genes confer cisplatin resistance in D. discoideum and in human cells, raised interest in the resistance mechanisms and their implications for cisplatin chemotherapy. Here we used expression microarrays to monitor physiological change...

Cisplatin is one of the most commonly used therapeutic drugs for cancer therapy, yet prolonged cisplatin treatment frequently results in drug resistance. To enhance therapeutic effect of cisplatin, we conducted a high throughput screening using a kinase library containing 704 kinases against triple negative breast cancer (TNBC) cells. We demonstrated that cisplatin activates ATR, CHK1 and WEE1,...

Resistance to cisplatin is a major problem in the treatment of solid tumors. To investigate the determinants of cisplatin resistance, we have identified cisplatin-inducible genes by differential display of mRNA. One of the cisplatin-inducible genes was identified as activating transcription factor 4 (ATF4). Northern blot analysis demonstrated that expression of ATF4 is inducible at the transcri...

Resistance to cisplatin is a major problem in the treatment of solid tumors. To investigate the determinants of cisplatin resistance, we have identified cisplatin-inducible genes by differential display of mRNA. One of the cisplatin-inducible genes was identified as activating transcription factor 4 (ATF4). Northern blot analysis demonstrated that expression of ATF4 is inducible at the transcri...

Resistance to the cytotoxic effects of cisplatin can be mediated through changes in a wide variety of cellular processes and signalling pathways. The discovery of microRNAs as regulators of protein expression through the targeting of mRNA has led to a number of studies on the effect of cisplatin treatment on microRNA expression, and the ability of microRNAs to modulate cisplatin resistance.

Chemotherapeutic agents are generally used as a frontline therapy for non-small cell lung cancer (NSCLC). However, resistance to chemotherapy arises rapidly in NSCLC, and the reasons for chemotherapy resistance have not been fully determined. Here, we found cisplatin, but not paclitaxel and doxorubicin, induced the enrichment of cancer stem cell (CSC) and conferred multidrug resistance in NSCLC...

Small cell lung cancer (SCLC) is the most aggressive lung-cancer subtype and so far, no favorable therapeutic strategy has been established for chemo-resistant SCLC. Cisplatin is one of the most important components among all standard poly-chemotherapeutic regimens for SCLC; therefore, this study focused on revealing Cisplatin-resistance mechanism(s) in this disease. Cisplatin-resistant SCLC ce...

We established three cis-diamminedichloroplatinum(II) (cisplatin)-resistant cell lines, T24/DDP5, T24/DDP7, and T24/DDP10, by the stepwise exposure of T24 human bladder cancer cells to increasing concentrations of cisplatin. The resistance to cisplatin of T24/DDP5, T24/DDP7, and T24/DDP10 cells was 2.2-, 5.2-, and 8.4-fold that of the parental T24 cells, respectively. The cisplatin-resistant ce...