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An adsorptive transfer technique coupled with brdicka reaction to reveal the importance of metallothionein in chemotherapy with platinum based cytostatics.

Krizkova S, Fabrik I, Huska D, Adam V, Babula P, Hrabeta J, Eckschlager T, Pochop P, Darsova D, Kukacka J, Prusa R, Trnkova L, Kizek R - Int J Mol Sci (2010)

Bottom Line: The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents.This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo.The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic.

ABSTRACT
The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents. Thanks to many clinical studies it is known that resistance of tumor cells to drugs is a frequent cause of chemotherapy failure. With regard to platinum based drugs, multidrug resistance can also be connected with increased expression of low-molecular weight protein metallothionein (MT). This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo. The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT. Further, we analyzed extracts of neuroblastoma cell lines treated with cisplatin or carboplatin. It is clear that neuroblastoma UKF-NB-4 cisplatin-resistant and cisplatin-sensitive cell lines unlikely respond to the presence of the platinum-based cytostatics cisplatin and carboplatin. Finally, we determined the level of MT in samples from rabbits treated with carboplatin and patients with retinoblastoma treated with the same drug.

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AdTS DP voltammograms of MT modified HMDE in the presence of pharmaceutical therapeutics containing cytostatic substances carboplatin (left panel) and cisplatin (right panel). MT and platinum-based cytostatics concentration 0.4 μg/mL; time of interaction MT with HMDE 120 s.
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f4-ijms-11-04826: AdTS DP voltammograms of MT modified HMDE in the presence of pharmaceutical therapeutics containing cytostatic substances carboplatin (left panel) and cisplatin (right panel). MT and platinum-based cytostatics concentration 0.4 μg/mL; time of interaction MT with HMDE 120 s.

Mentions: MT (0.4 μg/mL) modified HMDE was utilized for studying its interactions with cisplatin and carboplatin. For both compounds we obtained characteristic voltammograms (Figure 3). It clearly follows from the obtained results that the catalytic signal Cat2 diminished with increasing interaction time. After 20 min, the Cat2 signal decreased by more than 60% for both cytostatics. With increasing interaction times, no decrease of the signal was observed. For both drugs similar results were obtained, but the decrease of the signal was more rapid for cisplatin; where after 15 min interaction no further decrease of the signal was observed. For carboplatin, the decrease of the signal was slower and the lowering of the signal was complete after 20 min interaction. Similar results were obtained for interactions between cisplatin or carboplatin drugs, but a more distinct Cat2 signal decrease was observed after 10 min interaction for carboplatin and after 5 min for cisplatin (Figure 4).


An adsorptive transfer technique coupled with brdicka reaction to reveal the importance of metallothionein in chemotherapy with platinum based cytostatics.

Krizkova S, Fabrik I, Huska D, Adam V, Babula P, Hrabeta J, Eckschlager T, Pochop P, Darsova D, Kukacka J, Prusa R, Trnkova L, Kizek R - Int J Mol Sci (2010)

AdTS DP voltammograms of MT modified HMDE in the presence of pharmaceutical therapeutics containing cytostatic substances carboplatin (left panel) and cisplatin (right panel). MT and platinum-based cytostatics concentration 0.4 μg/mL; time of interaction MT with HMDE 120 s.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3100849&req=5

f4-ijms-11-04826: AdTS DP voltammograms of MT modified HMDE in the presence of pharmaceutical therapeutics containing cytostatic substances carboplatin (left panel) and cisplatin (right panel). MT and platinum-based cytostatics concentration 0.4 μg/mL; time of interaction MT with HMDE 120 s.
Mentions: MT (0.4 μg/mL) modified HMDE was utilized for studying its interactions with cisplatin and carboplatin. For both compounds we obtained characteristic voltammograms (Figure 3). It clearly follows from the obtained results that the catalytic signal Cat2 diminished with increasing interaction time. After 20 min, the Cat2 signal decreased by more than 60% for both cytostatics. With increasing interaction times, no decrease of the signal was observed. For both drugs similar results were obtained, but the decrease of the signal was more rapid for cisplatin; where after 15 min interaction no further decrease of the signal was observed. For carboplatin, the decrease of the signal was slower and the lowering of the signal was complete after 20 min interaction. Similar results were obtained for interactions between cisplatin or carboplatin drugs, but a more distinct Cat2 signal decrease was observed after 10 min interaction for carboplatin and after 5 min for cisplatin (Figure 4).

Bottom Line: The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents.This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo.The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic.

ABSTRACT
The drugs based on platinum metals represent one of the oldest, but also one of the most effective groups of chemotherapeutic agents. Thanks to many clinical studies it is known that resistance of tumor cells to drugs is a frequent cause of chemotherapy failure. With regard to platinum based drugs, multidrug resistance can also be connected with increased expression of low-molecular weight protein metallothionein (MT). This study aimed at investigating the interactions of MT with cisplatin or carboplatin, using the adsorptive transfer technique coupled with differential pulse voltammetry Brdicka reaction (AdTS DPV Brdicka reaction), and a comparison of in vitro results with results obtained in vivo. The results obtained from the in vitro study show a strong affinity between platinum based drugs and MT. Further, we analyzed extracts of neuroblastoma cell lines treated with cisplatin or carboplatin. It is clear that neuroblastoma UKF-NB-4 cisplatin-resistant and cisplatin-sensitive cell lines unlikely respond to the presence of the platinum-based cytostatics cisplatin and carboplatin. Finally, we determined the level of MT in samples from rabbits treated with carboplatin and patients with retinoblastoma treated with the same drug.

Show MeSH
Related in: MedlinePlus