Novel Soluble Cationic <i>trans</i>-Diaminedichloroplatinum(II) Complexes that Are Active against Cisplatin Resistant Ovarian Cancer Cell Lines

Najajreh, Yousef; Pérez, Jose; Navarro‐Ranninger, Carmen; Gibson, Dan

doi:10.1021/jm0201969

Cited by 106 publications

(83 citation statements)

References 16 publications

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“…Indeed, the sglAOE cells are more sensitive to carboplatin and the sglA⌬ cells are more resistant. It will be interesting to see if this relationship holds for the many cisplatin analogs, which have a wide range of toxicities and structures (31). In contrast to the platinum drugs, the sglAOE and sglA⌬ cells did not show altered sensitivity to doxorubicin (DNA intercalator and topoisomerase II inhibitor [2,5]), 5-FU (inhibits thymidylate synthase and incorporation of fluordeoxyuridine triphosphates into DNA [22]), and eto- poside (topoisomerase II inhibitor [35]).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Sphingosine-1-Phosphate Lyase or Inhibition of Sphingosine Kinase in Dictyostelium discoideum Results in a Selective Increase in Sensitivity to Platinum-Based Chemotherapy Drugs

et al. 2004

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The efficacy of the chemotherapy drug cisplatin is often limited due to resistance of the tumors to the drug, and increasing the potency of cisplatin without increasing its concentration could prove beneficial. A previously characterized Dictyostelium discoideum mutant with increased resistance to cisplatin was defective in the gene encoding sphingosine-1-phosphate (S-1-P) lyase, which catalyzes the breakdown of S-1-P, an important regulatory molecule in cell function and development and in the regulation of cell fate. We hypothesized that the increased resistance to cisplatin was due to an elevation of S-1-P and predicted that lowering levels of S-1-P should increase sensitivity to the drug. We generated three strains that stably overexpress different levels of the S-1-P lyase. The overexpressor strains have reduced growth rate and, confirming the hypothesis, showed an expression-dependent increase in sensitivity to cisplatin. Consistently, treating the cells with D-erythro-N,N,-dimethylsphingosine, a known inhibitor of sphingosine kinase, increased the sensitivity of mutant and parent cells to cisplatin, while addition of exogenous S-1-P or 8-Br-cyclic AMP made the cells more resistant to cisplatin. The increased sensitivity of the overexpressors to cisplatin was also observed with the cisplatin analog carboplatin. In contrast, the response to doxorubicin, 5-flurouracil, or etoposide was unaffected, indicating that the involvement of the sphingolipid metabolic pathway in modulating the response to cisplatin is not part of a global genotoxic stress response. The augmented sensitivity to cisplatin appears to be the result of an intracellular signaling function of S-1-P, because D. discoideum does not appear to have endothelial differentiation growth (EDG/S1P) receptors. Overall, the results show that modulation of the sphingolipid pathway at multiple points can result in increased sensitivity to cisplatin and has the potential for increasing the clinical usefulness of this important drug.

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Section: Discussionmentioning

confidence: 99%

Overexpression of Sphingosine-1-Phosphate Lyase or Inhibition of Sphingosine Kinase in Dictyostelium discoideum Results in a Selective Increase in Sensitivity to Platinum-Based Chemotherapy Drugs

et al. 2004

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“…Furthermore, in the interest of finding improved alternatives to cisplatin in second or third line treatment, the activity of the compounds in the A2780 and A2780res cell lines was compared (Table 6). In the A2780res cell line decreased uptake of cisplatin is observed as well as enhanced DNA repair, increased DNA damage tolerance and elevated glutathione (GSH) levels compared to the parent cell line A2780 [44]. As a result cisplatin shows an 8-fold decrease in activity in the A2780res compared to the A2780 cell line as shown in Table 6 as the resistance factor (RF).…”

Section: Cytotoxicity Propertiesmentioning

confidence: 99%

Three new asymmetric trans-amine(azole)dichloridoplatinum complexes that overcome cisplatin resistance and their reactions with 5′-GMP

Pantoja

Gallipoli

Zutphen

et al. 2006

Journal of Inorganic Biochemistry

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Three new asymmetric platinum(II) complexes comprising an isopropylamine ligand trans to an azole ligand were synthesized and fully characterized by 1 H NMR, 195 Pt NMR, IR and elemental analysis. In addition the X-ray crystal structure of all three complexes was determined. The reaction kinetics of the complexes with DNA model base guanosine-5 0 -monophosphate (GMP) was studied, revealing reaction kinetics comparable to cisplatin. To gain insight in the complexes as potential antitumor agents, cytotoxicity assays were performed on a variety of human tumor cell lines. These assays showed the complexes all to possess cytotoxicity profiles comparable to cisplatin. Furthermore, the complexes largely retain their activity in a human ovarian carcinoma cell line resistant to cisplatin, A2780R, compared to the cisplatin sensitive parent cell line A2780. These results are of fundamental importance, illustrating how platinum complexes of trans geometry can show improved activity compared to cisplatin in both cisplatin sensitive and cisplatin resistant cell lines.

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“…Palladium complexes with aromatic N-containing ligands, e.g., derivatives of pyridine, quinoline, pyrazole, and 1,10-phenanthroline, have shown very promising antitumor characteristics [1][2][3][4]. Some of these complexes, especially the trans analogs with nonplanar heterocyclic amine ligands, have been found to overcome multifactorial cisplatin resistance in human ovarian cell lines [5,6]. On the other hand, Pd(II) complexes have been widely explored due to their catalytic efficiency, e.g., for various carbon-carbon and carbon-nitrogen bond-forming reactions [7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Spectroscopic, structure and DFT studies of palladium(II) complexes with pyridine-type ligands

Małecki

Maroń

2011

Transition Met Chem

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Five palladium(II) complexes with pyridine derivative ligands have been synthesized. The molecular structures of the complexes were determined by X-ray crystallography, and their spectroscopic properties were studied. Based on the crystal structures, computational investigations were carried out in order to determine the electronic structures of the complexes. The electronic spectra were calculated with the use of time-dependent DFT methods, and the electronic spectra of the transitions were correlated with the molecular orbitals of the complexes. The emission properties of the complexes have been examined.

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Novel Soluble Cationic trans-Diaminedichloroplatinum(II) Complexes that Are Active against Cisplatin Resistant Ovarian Cancer Cell Lines

Cited by 106 publications

References 16 publications

Overexpression of Sphingosine-1-Phosphate Lyase or Inhibition of Sphingosine Kinase in Dictyostelium discoideum Results in a Selective Increase in Sensitivity to Platinum-Based Chemotherapy Drugs

Overexpression of Sphingosine-1-Phosphate Lyase or Inhibition of Sphingosine Kinase in Dictyostelium discoideum Results in a Selective Increase in Sensitivity to Platinum-Based Chemotherapy Drugs

Three new asymmetric trans-amine(azole)dichloridoplatinum complexes that overcome cisplatin resistance and their reactions with 5′-GMP

Spectroscopic, structure and DFT studies of palladium(II) complexes with pyridine-type ligands

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