Cisplatin cell culture

Primary renal cell culture has been utilized to study a number of nephrotoxic agents including mercuric chloride (Inamoto et al., 1976), cadmium (Cherian, 1982), lead (McLachlin et al., 1980), cisplatin (Tay et al., 1988), aminoglycoside antibiotics... 

It is possible that cisplatin cytotoxicity arises from more subtle effects than just general inhibition of transcription. The expression of some genes with a strong promoter is inhibited more in cultured cells by cisplatin than bulk RNA synthesis, and this differential sensitivity was not observed for trans-DDP [157][158], On the other hand, the induction of several weak promoters by cisplatin is reminiscent of the bacterial SOS response [158] [159]. Since the inhibition or activation of RNA polymerase II-medi-ated transcription by cisplatin is gene-specific and modulated by the promoter region, the end result would not be to shut down the cellular machinery so much as to create an imbalance. The selective inhibition, or induction, of gene expression by cisplatin is particularly relevant with respect to the expression of oncogenes, several of which have been implicated in cisplatin resistance [25],... 

N-NMR spectroscopy can be useful for ammine and amine complexes, but 14N is a quadrupolar nucleus, and quadrupolar relaxation is dominant when the environment of 14N has a low symmetry. This can lead to very broad lines and a consequent reduction in sensitivity. On the other hand, short relaxation times also have the advantage of allowing rapid pulsing so that a large number of transients can be acquired. Thus it is possible to follow reactions of cisplatin in blood plasma and cell-culture media at milli-molar drug concentrations and to detect ammine release [6],... 

In primary rahhit proximal tuhular (RPT) cells cisplatin exposure resulted in an inhihition of DNA synthesis, which is most likely related to the primary anti-tumorigenic mechanism of this compound i.e. DNA inter and intra strand cross linking [117]. RNA and protein synthesis were decreased in RPT cells and quiescent LLC-PK cells upon cisplatin exposure [117, 118]. Other effects of cisplatin on cultured RPT include a decrease in glucose uptake, an inhihition of Na -K ATPase and alterations in total glutathione content [117]. In the normal rat kidney (NRK) cell hne cisplatin (IpM for 48h) induced a marked increase in the level of lipid peroxides [119]. 

Fig. 1. The 500-MHz Hahn spin-echo H NMR spectra of a cell culture medium, Dulbecco s minimal essential medium, before (A) and after (B) reaction with 400 iiM cisplatin for 24 hr at 37°C, and after (C) reaction with Pt(en)Cl2l. Note the disappearance of the singlet at 2,14 ppm for the S-methyl of L-Met, which has formed Pt-Met complexes, giving new peaks at —2.7 ppm. (Adapted from Ref. 23.)...

In mouse mammary tumor cells, treatment with black cohosh increased the cytotoxicity of doxorubicin and docetaxel and decreased the cytotoxicity of cisplatin, but did not alter the effects of radiation or 4-hydroperoxycyclophos-phamide (an analog of cyclophosphamide that is active in cell culture) (Rockwell et al. 2005). 

The thioredoxin system, composed of nicotinamide adenine dinucleotide phosphate (reduced form), thioredoxin and thioredoxin reductase, may be involved in the cellular sensitivity to cis-diamminedichloroplatinum (Sasada et al. 1999). HeLa cells cultured with cisplatin showed a time-and dose-dependent reduction of intracellular thioredoxin reductase activity, which was well correlated with the decrease in cell viability after exposure to cisplatin. In a cell-free system, cisplatin was found to directly inactivate the reduced form of purified human thioredoxin reductase. The cis-platin-resistant variants of HeLa cells, estabUshed by continuous exposure to cisplatin, exhibited an increased expression and activity of thioredoxin reductase as well as thioredoxin compared with the... 

Cell cycle cytotoxity - in vitro (G1 and G2 + M Phases, cell culture) at 100.0 pg/mL, CA-Ovarian-O-342 and CA-Ovarian-O-342/Cisplatin resistant (G2 Phase, cell culture) in vitro at 2.0 pM, Leuk-P388 and Leuk-P388 (ADR-resistant). Compound enhanced effect of adriamydn or effect seen only when compound and adriamydn exposure were concurrent. Cytotoxic - in vitro (Cell culture, Leuk-L1210), cone, used not stated sarcoma-9 and cells-monkey-kidney-CV-1 (at 50.0 pg/mL). 

Cytotoxic - in vitro (Cell culture) vs. CA-Ovarian-O-342 (IC50 24.0 pg/mL), CA-Ovarian-O-342/Cisplatin resistant (IC50 12.0 pg/mL). In both case effects seen enhanced by hyperthermia. 

---