Activity profile of the cisplatin analogue PN149 in different tumor cell lines

Comparative Study of the Mode of Action of Clinically Approved Platinum-Based Chemotherapeutics

“…The impact of carboplatin and oxaliplatin on the gene expression profiles of genes related to genomic stability was investigated in A498 cells using high-throughput RT-qPCR [14]. The results are summarized in a heatmap in Figure 3 and compared to gene expression profiles already established for cisplatin [13]. Relative gene expressions were calculated by normalizing the treated samples to the untreated control, and are expressed as log2 values.…”

“…Induction of the cell cycle related genes CDKN1A, CCND1, PLK3 and PPMID and the apoptosis related genes BBC3, APAF1, PMAIP1 and TNFRSF10B suggested modulation of the respective pathway by the platinum drugs. DAPI staining and flow cytometry was therefore used for functional analysis of cell cycle regulation and apoptosis upon treatment with carboplatin and oxaliplatin, and the results were compared to data established for cisplatin [13]. A498 cells were treated with the respective compound for 1 h and cell cycle distribution was measured after a 24, 48, 72 and 96 h recovery period.…”

“…The proximale tubule is also the site of cisplatin-induced damage and inflammation, which is the underlying cause of dose-limiting severe nephrotoxicity observed for this drug. The mode of action of cisplatin was investigated using A498 cells and published previously [13]; data relevant to the current investigation are included in the present study for comparison. The cellular activity of platinum drugs was analyzed on the transcriptional level using gene expression analysis, and observations on the transcriptional level were further examined at the functional level for confirmation.…”

Nitroxyl as a Potential Theranostic in the Cancer Arena

“…This study provides the evidence that PNCs may be more effective for tumors that have developed resistance to cisplatin. The same research group has revealed that platinum(IV)-HNO complex PN149 treatment causes cell cycle arrest and cell apoptosis in the bladder cancer cells and the renal cell carcinoma cells (125). Application of PN149 stimulates the oxidative-stress-sensitive genes, including ferritin heavy chain 1, glutamate-cysteine ligase catalytic, Nrf2, HO-1, and thioredoxin reductase 1 in RT112 cells, but not A498 cells (125), suggesting a cell-type specific activation.…”

“…The same research group has revealed that platinum(IV)-HNO complex PN149 treatment causes cell cycle arrest and cell apoptosis in the bladder cancer cells and the renal cell carcinoma cells (125). Application of PN149 stimulates the oxidative-stress-sensitive genes, including ferritin heavy chain 1, glutamate-cysteine ligase catalytic, Nrf2, HO-1, and thioredoxin reductase 1 in RT112 cells, but not A498 cells (125), suggesting a cell-type specific activation. In addition, infusion of a HNO derivative pirolin protects the rat brain against the toxic effects of oxidative stress and inflammation response induced by the anticancer drugs doxorubicin (DOX), paclitaxel, and docetaxel (DTX), thus highlighting HNO as a potential drug against these anticancer drugevoked brain oxidative damage (147).…”