New imidazole-coordinated chemotherapeutics with low epithelial toxicity
Tóm tắt
The new imidazole-coordinated chemotherapeutics with low epithelial toxicity (NICE) presented in this article feature innovative drugs that combine epithelial toxicity comparable with that of carboplatin with novel carrier ligands optimized for DNA interaction. Recent identification of the pivotal role of basolateral organic cation transporters (OCTs) in cisplatin nephrotoxicity by a new model system (electrical resistance breakdown assay) facilitated the search for substances with a favorable organotoxic profile. The assay uses the high transepithelial electrical resistance (TEER) of the C7-clone of Madin-Darby canine kidney (MDCK) cells and the exclusive basolateral expression of OCT2 in these cells. TEER and caspase-3 activity of MDCK-C7-cells grown on microfilter membranes were monitored in response to exposure of either the apical or basolateral plasma membrane to platinum complexes. The impact of complexes on cancer cell lines was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bomide tests. Effects of substituents on pharmacological properties of NICE were systematically investigated by introducing sterically demanding groups as well as electron-donating and electron-withdrawing groups. Derivatives of NICE showed different renal epithelial toxic profiles and effects on cancer cells. NICE were significantly less toxic than cis-or oxaliplatin. The chlorine substituted NICE had no effect on epithelial integrity but markedly cytotoxic activity against amelanotic melanoma cells. Together, side effect targeted screening for new anticancer drugs with the electrical resistance breakdown assay offers an interesting approach for identifying and investigating new compounds. NICE feature the first group of platinum-based cytostatics discovered by using this system for systematic screening of new chemotherapeutics with low renal epithelial toxicity.
Tài liệu tham khảo
Rosenberg, B., Vancamp, I., and Krigas, T. (1965) Inhibition of cell division in escherichia coli by electrolysis products from a platinum electrode. Nature 205, 698–699.
Rosenberg, B., Vancamp, I., Trosko, J. E., and Mansour, V. H. (1969) Platinum compounds: a new class of potent antitumour agents. Nature 222, 385–386.
Lebwohl, D., and Canetta, R. (1998) Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. Eur. J. Cancer 34, 1522–1534.
Schaefer, S. D., Post, J. D., Close, L. G., and Wright, C. G. (1985) Ototoxicity of low- and moderate-dose cisplatin. Cancer 56, 1934–1939.
Goren, M. P., Wright, R. K., and Horowitz, M. E. (1986) Cumulative renal tubular damage associated with cisplatin nephrotoxicity. Cancer Chemother. Pharmacol. 18, 69–73.
Hartmann, J. T., and Lipp, H. P. (2003) Toxicity of platinum compounds. Expert Opin. Pharmacother. 4, 889–901.
Wong, E., and Giandomenico, C. M. (1999) Current status of platinum-based antitumor drugs. Chem. Rev. 99, 2451–2466.
Ho, Y. P., Au-Yeung, S. C., and To, K. K. (2003) Platinum-based anticancer agents: innovative design strategies and biological perspectives. Med. Res. Rev. 23, 633–655.
Go, R. S., and Adjei, A. A. (1999) Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. J. Clin. Oncol. 17, 409–422.
Lokich, J., and Anderson, N. (1998) Carboplatin versus cisplatin in solid tumors: an analysis of the literature. Ann. Oncol. 9, 13–21.
Mulder, P. O., Sleijfer, D. T., de Vries, E. G., Uges, D. R., and Mulder, N. H. (1988) Renal dysfunction following high-dose carboplatin treatment. J. Cancer Res. Clin. Oncol. 114, 212–214.
Pera, M. F., Jr., Zook, B. C., and Harder, H. C. (1979) Effects of mannitol or furosemide diuresis on the nephrotoxicity and physiological disposition of cis-dichlorodiammine-platinum-(II) in rats. Cancer Res. 39, 1269–1278.
Safirstein, R., Winston, J., Goldstein, M., Moel, D., Dikman, S., and Guttenplan, J. (1986) Cisplatin nephrotoxicity. Am. J. Kidney Dis. 8, 356–367.
Tsuruya, K., Ninomiya, T., Tokumoto, M., et al. (2003) Direct involvement of the receptor-mediated apoptotic pathways in cisplatin-induced renal tubular cell death. Kidney Int. 63, 72–82.
Park, M. S., De Leon, M., and Devarajan, P. (2002) Cisplatin induces apoptosis in LLC-PK1 cells via activation of mitochondrial pathways. J. Am. Soc. Nephrol. 13, 858–865.
Somani, S. M., Husain, K., Whitworth, C., Trammell, G. L., Malafa, M., and Rybak, L. P. (2000) Dose-dependent protection by lipoic acid against cisplatin-induced nephrotoxicity in rats: antioxidant defense system. Pharmacol. Toxicol. 86, 234–241.
Brady, H. R., Kone, B. C., Stromski, M. E., et al. (1990) Mitochondrial injury: an early event in cisplatin toxicity to renal proximal tubules. Am. J. Physiol. 258, F1181-F1187.
Lau, A. H. (1999) Apoptosis induced by cisplatin nephrotoxic injury (1999) Kidney Int. 56, 1295–1298.
Ramesh, G., and Reeves, W. B. (2002) TNF-alpha mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J. Clin. Investig., 110, 835–842.
Binks, S. P., and Dobrota, M. (1990) Kinetics and mechanism of uptake of platinum-based pharmaceuticals by the rat small intestine. Biochem. Pharmacol. 40, 1329–1336.
Ghezzi, A., Aceto, M., Cassino, C., Gabano, E., and Osella, D. (2004) Uptake of antitumor platinum(II)-complexes by cancer cells, assayed by inductively coupled plasma mass spectrometry (ICP-MS). J. Inorg. Biochem. 98, 73–78.
Cesar, E. T., de Almeida, M. V., Fontes et al. (2003) Synthesis, characterization, cytotoxic activity, and cellular accumulation of dinuclear platinum complexes derived from N,N′-di-(2-aminoethyl)-1,3-diamino-2-propanol, aryl substituted N-benzyl-1,4-butanediamines, and N-benzyl-1,6-hexanediamines. J. Inorg. Biochem. 95, 297–305.
Ludwig, T., Riethmuller, C., Gekle, M., Schwerdt, G., and Oberleithner, H. (2004) Nephrotoxicity of platinum complexes is related to basolateral organic cation transport. Kidney Int. 66, 196–202.
Ludwig, T., Fakih, S., Krebs, B., and Oberleithner, H. (2004) Platinum complex cytotoxicity tested by the electrical resistance breakdown assay. Cell Physiol. Biochem. 14, 425–430.
Ludwig, T., and Oberleithner, H. (2004) Platinum complex toxicity in cultured renal epithelia. Cell Physiol. Biochem. 14, 431–440.
Shu, Y., Bello, C. L., Mangravite, L. M., Feng, B., and Giacomini, K. M. (2001) Functional characteristics and steroid hormone-mediated regulation of an organic cation transporter in Madin-Darby canine kidney cells. J. Pharmacol. Exp. Ther. 299, 392–398.
Gekle, M., Wunsch, S., Oberleithner, H., and Silbernagl, S. (1994) Characterization of two MDCK-cell subtypes as a model system to study principal cell and intercalated cell properties. Pflugers Arch. 428, 157–162.
Wunsch, S., Gekle, M., Kersting, U., Schuricht, B., and Oberleithner, H. (1995) Phenotypically and karyotypically distinct Madin-Darby canine kidney cell clones respond differently to alkaline stress. J. Cell. Physiol. 164, 164–171.
Ludwig, T., Ossig, R., Graessel, S., Wilhelmi, M., Oberleithner, H., and Schneider, S. W. (2002) The electrical resistance breakdown assay determines the role of proteinases in tumor cell invasion. Am. J. Physiol. Renal Physiol. 283, F319-F327.
Cummings, B.S., and Schnellmann, R. G. (2002) Cisplatin-induced renal cell apoptosis: caspase 3-dependent and-independent pathways. J. Pharmacol. Exp. Ther. 302, 8–17.
Olver, I., Green, M., Peters, W., Zimet, A., Toner, G., Bishop, J., Ketelbey, W., Rastogi, R., and Birkhofer, M. (1995) A phase II trial of zeniplatin in metastatic melanoma. Am. J. Clin. Oncol. 18, 56–58.
Monti, E., Gariboldi, M., Maiocchi, A. et al. (2005) Cytotoxicity of cis-platinum(II) conjugate models. The effect of chelating arms and leaving groups on cytotoxicity: a quantitative structure-activity relationship approach. J. Med. Chem. 48, 857–866.
Yao, S. W., Lopes, V. H., Fernandez, F., et al. (2003) Synthesis and QSAR study of the anticancer activity of some novel indane carbocyclic nucleosides. Bioorg. Med. Chem. 11, 4999–5006.
Friebolin, W., Schilling, G., Zoller, M., and Amtmann, E. (2004) Synthesis and structure-activity relationship of novel antitumoral platinum xanthate complexes. J. Med. Chem. 47, 2256–2263.
Ren, S., Wang, R., Komatsu, K., et al. (2002) Synthesis, biological evaluation, and quantitative structure-activity relationship analysis of new Schiff bases of hydroxy-semicarbazide as potential antitumor agents. J. Med. Chem. 45, 410–419.
Wanchana, S., Yamashita, F., and Hashida, M. (2003) QSAR analysis of the inhibition of recombinant CYP 3A4 activity by structurally diverse compounds using a genetic algorithm-combined partial least squares method. Pharm. Res. 20, 1401–1408.
Kelland, L. R. (2000) Preclinical perspectives on platinum resistance. Drugs 59 (Suppl) 4, 1–8.
Ludwig, T., Puttmann, S., Bertram, H., et al. (2005) Functional measurement of local proteolytic activity in living cells of invasive and non-invasive tumors. J. Cell Physiol. 202, 690–697.
Schneider, S. W., Ludwig, T., Tatenhorst, L., et al. (2004) Glioblastoma cells release factors that disrupt blood-brain barrier features. Acta Neuropathol. (Berl) 107, 272–276.
Zak, J., Schneider, S. W., Eue, I., Ludwig, T., and Oberleithner, H. (2000) High-resistance MDCK-C7 monolayers used for measuring invasive potency of tumour cells. Pflugers Arch. 440, 179–183.
Lieberthal, W., Triaca, V., and Levine, J. (1996) Mechanisms of death induced by cisplatin in proximal tubular epithelial cells: apoptosis vs. necrosis. Am. J. Physiol. 270, F700-F708.
Zucker, R. M., Elstein, K. H., Easterling, R. E., and Massaro, E. J. (1988) Metal-induced alteration of the cell membrane/cytoplasm complex studied by flow cytometry and detergent lysis. Toxicology 53, 69–78.