Abstract
The uptake kinetics of cisplatin analogs of 1,2-cyclohexanediamine(dach) isomers with various leaving groups, by human erythrocytes in plasma isotonic buffer, were studied. The experimental results showed that the uptake rate constants (k values) decrease with the change of leaving group in the sequence: chloride (Cl) > squaric acid (SA) > oxalate (OX) > demethylcantharic acid (DA), with the same dach isomer as carrier group. It is noteworthy that for the platinum (II) complexes with the same leaving group, the k values always reduce as: 1R, 2R-dach > 1R, 2S-dach > 1S, 2S-dach. This result reflects the chirality selectivity. No differences in reactivity to protein thiols and effects on membrane permeability were found for the R,R-, R,S-, S,S-isomeric complexes. It is proposed that the chirality selectivity in uptake is due to the recognition of the chirality of the platinum complexes by the erythrocyte membrane. The interactions between the chiral platinum complexes and the head groups of the membrane phospholipid molecules are probably involved.
Similar content being viewed by others
References
Dodge JT, Mitchell C, Hanahan DJ. 1963 The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes. Arch Biochem Biophys 100, 119–130.
Ellman GL. 1959 Tissue sulfhydryl groups. Arch Biochem Biophys 82, 70–77.
Gately DP, Howell SB. 1993 Cellular accumulation of the anticancer agent cisplatin: a review. Br J Cancer 67, 1171–1176.
Inagaki K, Kidani Y. 1986 Difference in binding of (1,2-cyclohexanediamine) platinum(II) isomers with d(GpG). Inorg Chem 25, 1–3.
Inagaki K, Nakahara H, Alink M, Kidani Y. 1990 Characterization of (1,2-cyclohexanediamine) platinum( II) isomers and their d(GpG) adducts by means of 1H NMR spectroscopy. Inorg Chem 29, 4496–4500.
Keith AD, Bulfield G, Snipes W. 1970 Spin-labeled neurospora mitochondria. Biophys J 10, 618–629.
Kidani Y, Noji M. 1991 Developmental approach to prepare new types of antitumor platinum complexes with dual function. In: Howell SB, ed. Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy. New York: Plenum Press; 127–137.
Kornberg RD, McConnell HM. 1971 Inside-outside transitions of phospholipids in vesicle membranes. Biochemistry 10, 1111–1120.
Lammel B, Maier G. 1980 A spin labeling study of the effects of inorganic ions and pH on the conformation of spectrin. Biochim Biophys Acta 622, 245–258.
Lu JF, An PD, Ma YL, et al.1995a Study of permeability of cis-spin labeled platinum complexes through human erythrocyte membrane. Acta Biophysica Sinica 11, 195–200.
Lu JF, Wang K, Sun XZ, et al. 1995b Effects of cisplatin and its analogues on the permeability of human erythrocyte membrane. Metal-Based Drugs 2, 73–80.
Reile H, Bernhardt G, Koch M, et al. 1992 Chemosensitivity of human MCF-7 breast cancer cells to diastereoisomeric diaqua (1,2-diphenylethylenediamine) platinum (II) sulfates and specific platinum accumulation. Cancer Chemother Pharmacol 30, 113–122.
Sandberg HE, Bryant RG, Piette LH. 1969 Location of sulfhydryl groups in erythrocyte membranes with magnetic resonance spin probes. Arch Biochem Biophys 133, 144–152.
Speer RJ, Hall LM, Stewart DP, et al. 1978 Antitumor activity of platinum complexes of 1,2-diaminocyclohexane isomers. J Clin Hematol Oncol 8, 44–50.
Wang K, Lu JF, Li RC. 1996 Events happening when cisplatin molecules encounter the cell. Coord Chem Rev 151, 53–88.
Zhang WM, Li LZ, Li RC, et al.1993 The kinetic studies of across-erythrocyte membrane transport of platinum (II) complexes. Chemical J Chinese Univ 14, 1351–1353.
Zou J. 1995 Ph.D. thesis, Nanjing University, China.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zou, J., Yang, X.G., Li, R.C. et al. The chirality selectivity in the uptake of platinum (II) complexes with 1,2-cyclohexanediamine isomers as carrier ligand by human erythrocytes. Biometals 10, 37–43 (1997). https://doi.org/10.1023/A:1018314719904
Issue Date:
DOI: https://doi.org/10.1023/A:1018314719904