Effect of structural modification at the 4, 3′, and 2′ positions of doxorubicin on topoisomerase II poisoning, apoptosis, and cytotoxicity in human melanoma cells
Tóm tắt
The mechanism of the cytotoxicity of anthracyclines is pleiotropic and its significance in cell growth inhibition seems to be highly specific and dependent on cell type and anthracycline drug. Resistance and the high cardiotoxicity of anthracyclines have stimulated many studies aimed at identifying critical substituents required for optimal activity. Many authors point to the fact that the double-strand breaks, the consequence of the activity of topoisomerase II poisons, and the inability of cells to repair the DNA lesions are the signal for apoptosis. The aim of this study was to define the influence of 4-demetoxy 2′-halogenated analogs with altered basicity at the 3′-position on topoisomerase II and the relationship of that interaction with apoptosis and the cytotoxicity of these novel anthracyclines. Parental human ME18 melanoma cells and the ME18/R subline, obtained experimentally, resistant to doxorubicin (DOX), exposed to 1.7 and 8.6 µM DOX or its analogs, annamycin and WP903 (both 0.3 and 3.0 µM) were studied. The MTT test was used to assay cytotoxicity. Interaction of the drugs with topoisomerase II and apoptosis were done by Western blot and fluorescence microscopy using Hoechst 33342. The structural changes at positions 4, 2′, and 3′ can influence topoisomerase II interaction and apoptotic activity, although correlation between these events and cytotoxic consequences has not been proved. The biological response of the cells to the structurally similar anthracyclines may be variable and probably depends on the cell type which seems to be an additional problem in the multifactorial resistance of tumor cells to anthracyclines.
Tài liệu tham khảo
Anuszewska E. L., Gruber B. M. and Koziorowska J. H. (1997): Studies on adaptation to adriamycin in cells pretreated with hydrogen peroxide. Biochem. Pharmacol., 54, 597–603.
Arpino G., Ciocca D. R., Weiss H., Allred D. C., Daguerre P., Vargas-Roig L., Leuzzi M., Gago F., Elledge R. and Mohsi S. K. (2005): Predictive value of apoptosis, proliferation, HER-2, and topoisomerase II alpha for anthracycline chemotherapy in locally advanced breast cancer. Breast Cancer Res. Treat., 92, 69–75.
Capranico G., Supino R., Binaschi M., Capolongo L., Grandi M., Suarato A. and Zunino F. (1994): Influence of structural modifications at the 3′ and 4′ positions of doxorubicin on the drug ability to trap topoisomerase II and to overcome multidrug resistance. Mol. Pharmacol.. 45, 908–915.
Cardoso F., Durbecq V., Larsimont D., Paesmans M., Leroy J. Y., Rouas G., Sotiriou C., Renard N., Richard V., Piccart M. J. and Di Leo A. (2004): Correlation between complete response to anthracycline-based chemotherapy and topoisomerase II-alpha gene amplification and protein overexpression in locally advanced/metastatic breast cancer. Int. J. Oncol., 24, 201–209.
De Boer R. A., van Veldhuisen D. J., van der Wijk J., Brouwer R. M., de Jonge N., Cole G. M. and Suurmeijer A. J. (2000): Additional use of immunostaining for active caspase 3 and cleaved actin and PARP fragments to detect apoptosis in patient with chronic heart failure. J. Card. Fail., 6, 330–337.
Den Boer M. L., Pieters R. and Veerman A. J. (1998): Mechanisms of cellular anthracycline resistance in childhood acute leukemia. Leukemia, 12, 1657–1670.
De Graff W. G., Myers L. S. Jr., Mitchell J. B. and Hahn S. M. (2003): Protection against adriamycin cytotoxicity and inhibition of DNA topoisomerase II activity by 3,4-dihydroxybenzoic acid. Int. J. Oncol., 23, 159–163.
Di Leo A. and Isola J. (2003): Topoisomerase II alpha as a marker predicting the efficacy of anthracyclines in breast cancer: are we at the end of the beginning? Clin. Breast Cancer, 4, 179–186.
Durbecq V., Paesmans M., Cardoso F., Desmedt C., Di Leo A., Chan S., Friedrichs K., Pinter T., Van Belle S., Murray E., Bodrogi I., Walpole E., Lesperance B., Korec S. Crown J., Simmonds P., Perren T. J., Leroy J. Y., Rouas G., Sotiriou C., Piccart M. and Larsimont D. (2004): Topoisomerase II-alpha expression as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel. Mol. Cancer Ther., 3, 1207–1214.
Gariboldi M. B., Ravizza R., Riganti L., Meschini S., Calcabrini A., Marra M., Arancia G., Dolfini E. and Montie E. (2003): Molecular determinants of intrinsic resistance to doxorubicin in human cancer cell lines. Int. J. Oncol., 22, 1057–1064.
Gewirtz D. A. (1999): A critical evaluation of the mechanism of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem. Pharmacol., 57, 727–741.
Grabowski D. R., Dubyak G. R., Rybicki L., Hidaka H. and Ganapathi R. (1998): Tumor cell resistance to topoisomerase II poisons. Role for intracellular free calcium in the sensitization by inhibitors of calcium-calmodulin-dependent enzymes. Biochem. Pharmacol., 56, 345–349.
Gruber B. M., Anuszewska E. L., Bubko I., Goździk A., Priebe W. and Fokt I. (2005): Relationship between topoisomerase II-DNA cleavable complexes, apoptosis and cytotoxic activity of anthracyclines in human cervix carcinoma cells. Anticancer Res., 25, 2193–2198.
Gruber B. M., Anuszewska E. L. and Priebe W. (2004): The effect of new anthracycline derivatives on the induction of apoptotic processes in human neoplastic cells. Folia Histochem. Cytobiol., 42, 127–130.
Gruber B. M., Anuszewska E. L., Roman I., Goździk A., Priebe W. and Fokt I. (2006): Topoisomerase II alpha expression and cytotoxicity of anthracyclines in human neoplastic cells. Acta Pol. Pharm. Drug Res., 63, 15–18.
Jarvinen T. A. and Liu E. T. (2003): HER-2/neu and topoisomerase II alpha in breast cancer. Breast Cancer Res. Treat., 78, 299–311.
Koshiyama M., Fujii H., Kinezaki M. and Yoshida M. (2001): Correlation between topo II alpha expression and chemosensitivity testing for topo II-targeting drugs in gynaecological carcinomas. Anticancer Res., 21, 905–910.
Lage H. and Dietel M. (2002): Multiple mechanisms confer different drug resistant phenotypes in pancreatic carcinoma cells. J. Cancer Res. Clin Oncol., 128, 349–357.
Li T.-K. and Liu L. F. (2001): Tumor cell death induced by topoisomerase-targeting drugs. Annu. Rev. Pharmacol. Toxicol., 41, 53–77.
MacGrogan G., Rudolph P., Mascarel Id I., Mauriac L., Durand M., Avril A., Dilhuydy J. M., Robert J., Mathoulin-Pelissier S., Picot V., Floquet A., Sierankowski G. and Coindre J. M. (2003): DNA topoisomerase II alpha expression and the response to primary chemotherapy in breast cancer. Br. J. Cancer, 89, 666–671.
Martin-Richard M., Munoz M., Albanell J., Colomo L., Bellet M., Rey M. J., Tabernero J., Alonso C., Cardesa A., Gascon P. and Fernandez P. L. (2004): Serial topoisomerase II expression in primary breast cancer and response to neoadjuvant anthracycline-based chemotherapy. Oncology, 66, 388–394.
Nowak R. and Tarasiuk J. (2004): The inhibition of apoptosis in cancer cells resistant to anticancer drugs (in Polish). Postępy Biochem., 50, 330–341.
Priebe W. (1995): Mechanism of action-governed design of anthracycline antibiotics: a “turn-off/turn-on” approach. Curr. Pharm. Des., 1, 51–68.
Ramachandran Ch., Samy T. S., Huang X. L., Yuan Z. K. and Krishan A. (1993): Doxorubicin-induced DNA breaks, topoisomerase II activity and gene expression in human melanoma cells. Biochem. Pharmacol., 45, 1367–1371.
Sehested M. and Jensen P. B. (1996): Mapping of DNA topoisomerase II poisons (etoposide, clerocidin) and catalytic inhibitors (aclarubicin, ICRF-17) to four distinct steps in the topoisomerase II catalytic cycle. Biochem. Pharmacol., 51, 879–886.
Trevino A. V., Woynarowska B. A., Herman T. S., Priebe W. and Woynarowski J. M. (2004): Enhanced topoisomerase II targeting by annamycin and related 4-demethoxy anthracycline analogues. Mol. Cancer Ther., 3, 1403–1410.
Yamazaki K., Isobe H., Hanada T., Betsuyaku T., Hasegawa A., Hizawa N., Ogura S. and Kawakami Y. (1997): Topoisomerase II alpha content and topoisomerase II catalytic activity cannot explain drug sensitivities to topoisomerase II inhibitors in lung cancer cell lines. Cancer Chemother. Pharmacol., 39, 192–198.