Čes. slov. farm. 2006, 55(3):99-109
Cytotoxicity Screening and Mode of Action of Natural and Synthetically Prepared Compounds Usable in Tumour Chemotherapy
- 1 Fakulta chemickej a potravinárskej technológie Bratislava, Katedra biochémie a mikrobiológie
- 2 Slovenská technická univerzita Bratislava, Katedra organickej chémie
The paper reviews the current approaches to cytotoxic effect screening and mode of action of natural and synthetic compounds usable in tumour chemotherapy. Oncological diseases belong to the most frequently occurring and the most serious diseases that threaten millions of human lives. A serious complication of anticancer therapy is an inadequate therapeutic answer which is caused by the resistance of the human organism to the employed drugs, chemotherapeutic agents. Therefore the resistance is one of the driving forces which constantly force us to search for new anticancer effective drugs of natural or synthetic origin. Primary screening in vitro, in which by different methods the sensitivity of cancer cells growing in vitro to cytotoxic compounds is monitored, is commonly and routinely used for searching for new potential cytostatics today. The properties of a potential anticancer compound are characterized by different parameters, which include antiproliferative activity, monitoring of structural and functional changes in the cytoplasmic membrane, changes in cell proteins and nucleic acids content, cell metabolism changes, cell cycle changes, induction of apoptosis, enzymatic activity (dihydrofolate reductase, proteinases, proteinkinases, topoisomerases, tymidylatsynthetase), effect on mitochondria, cell cytoskeleton, telomerase activity, etc. By monitoring these parameters, the mode of action of a cytotoxically effective compound can be followed up.
Keywords: cancer cell transformation; cytotoxicity; cell death; cell cycle; cytoskeleton
Received: September 27, 2005; Accepted: March 1, 2006; Published: March 1, 2006 Show citation
References
- Kaušitz, J., Altaner, Č. et al.: In: Onkológia. Bratislava, VEDA, vydavateľstvo Slovenskej akadémie vied, 2003, s. 4-30, 83-85, 138-139.
- Altaner, Č.: In: Bunková a molekulárna biológia rakoviny. Bratislava, Liga proti rakovine, 2001, s. 10-21.
- Weinberg, R. A.: In: Jediná odrodilá buňka. Jak vzniká rakovina. Praha, ACADEMIA, 1998, s. 48-55.
- Ferenčík, M., Škárka B. et al.: In: Biochémia. Bratislava, Slovak Academic Press, 2000, s. 410-411.
- http://www.zdravcentra.sk/cps/rde/xchg/zcsk/xsl/3141_1488.html
- Klener, P.: In: Protinádorová chemoterapie. Praha, Galén, 1996, s. 80-83, 94, 112, 199-201, 278-279.
Go to original source...
- Fuery, C. J., Impey, H. L., Roberts, N. J. et al.: Clin. Chem., 2000; 46, s. 620-624.
Go to original source...
- Kliewer, S. A., Lehman, J., Willson, T.: Science, 1999; 284, s. 757-760.
Go to original source...
Go to PubMed...
- Kolář, Z.: http://www.lmp.upol.cz/download/receptory.ppt
- Hulín, I. et al.: In: Patofyziológia. Bratislava, SAP, 2002. s. 108, 214-216.
- Kliewer, S. A., Lehmann, J. M., Milburn, M. V. et al.: Recent Prog. Horm. Res., 1999; 54, s. 345-67.
- Kliewer, S. A., Xu, H. E., Lambert, M. H., Willson, T. M.: Recent Prog. Horm. Res., 2001; 56, s. 239-263.
Go to original source...
Go to PubMed...
- Bozec, A., Chuzel, F., Chater, S. et al.: J. Endocrinol., 2004; 183, s. 79-90.
Go to original source...
Go to PubMed...
- Alexander, B. T.: Am. J. Physiol. Regul. Integr. Comp. Physiol., 2003; 285, s. R933-R934.
Go to original source...
Go to PubMed...
- Wolfs, T. G., de Vries, B., Walter, S. J. et al.: Am. J. Transplant., 2005; 5, s. 68-75.
Go to original source...
Go to PubMed...
- http://www.clsjep.cz/Ukazclanek2.asp?clanek=14542& jazyk
- Salmon, S. E.: Cancer Treat. Rep., 1984; 68 (1), 117-125.
- Ferenčík, M., Rovenský, J., Nyulassy, Š.: Imunológia. In: Základné termíny a definície (Druhé prepracované a doplnené vydanie). Bratislava, Slovak Academic Press s.r.o., 2001, s. 26-27.
- Barile, F. A.: In: Introduction to in vitro cytotoxicology. Florida, USA, Mechanisms and methods. CRC Press, Boca Raton, 1994, s. 27-45.
- Kanďárová, H., Jantová, S., Hojerová, J.: Čes.-slov. Derm., 2004; 79 (2), 75-83.
- Roche Molecular Biochemicals. Apoptosis and Cell Proliferation. 2nd revised edition. s. 1-63.
- Denizot, F., Lang, R.: J. Immunol. Methods., 1986; 89 (2), 271-277.
Go to original source...
Go to PubMed...
- Jantová, S.: Cytotoxicita, antimikróbna aktivita a mechanizmus účinku prírodných a syntetických látok. Habilitačná práca. CHTF STU, 1999, s. 9-29.
- Pisha, E., Chai, H., Lee, I. S. et al.: Nature Med., 1995; 1, 1046-1051.
Go to original source...
Go to PubMed...
- Vopršalová, M., Žáčková, P.: In: Základy toxikologie pro farmaceuty. UK Praha, Nakladetelství Karolinum, 2000, s. 21-27.
- Horáková, K., Jantová, S.: Biológia. Bratislava, STU, 1998, s. 170-171.
- Barišič, K., Petrik, J., Rumora, L.: Acta Pharm., 2003; 53, 151 - 164.
- Babál, P.: Medicínsky monitor, 2003; 1, 1-9.
- Romero, D., Gomez-Zapata, M., Luna, A., Garcia-Fernandez A. J.: Toxicol. in Vitro, 2003; 17(3), 293-239.
Go to original source...
Go to PubMed...
- Boudreault, F., Grygorczyk, R.: J. Microsc., 2004; 215(3), 302-312.
Go to original source...
Go to PubMed...
- Zink, D., Andrew, H., Fischer, A. H., Nickerson, J. A.: Cancer, 2004; 4, 677-685.
Go to original source...
Go to PubMed...
- Putnam, K. P., Bombick, D. W., Doolittle, D. J.: Toxicol. in Vitro, 2002; 16(5), 599-607.
Go to original source...
Go to PubMed...
- Albrecht, C. F., Theron, E. J., Kruger, P. B.: S. Afr. Med. J., 1995; 85(9), 853-860.
Go to original source...
- Veselská, R., Zitterbart, K., Jelínková, Š. et al.: Oncol. Rep., 2003; 10, 1049-1058.
- Kanduc, D., Mittelman, A., Serpico, R. et al.: Inter. J. Oncol., 2002; 21, 165-170.
- Vermes, I., Haanen, C., Reutelingsperger, C.: J. Immunol. Methods, 200; 243 (1-2), 167-190.
- Jantová, S.: In: Chémia a život okolo nás. Bratislava, Vydavateľstvo STU, 2005, s. 108.
- An, W. W., Gong, X. F., Wang, M. W. et al.: Acta Pharmacol. Sin., 2004; 25 (11), 1502-1508.
- Borisenko, G. G., Matsura, T., Liu, S. X. et al.: 413 (1) 41-52.
- Dandrea, T., Hellmold, H., Jonsson, C. et al.: Free Radic Biol. Med., 2004; 36 (7), 881-896.
Go to original source...
Go to PubMed...
- Kim, S. D., Moon, C. K., Eun, S. Y. et al.: Biochem. Biophys. Res. Commun., 2005; 328 (1), 326-334.
Go to original source...
Go to PubMed...
- www.biomedcentral.com/ 1534-5874/2/39/figure/F2
- Thornberry, N. A., Lazebnik, Y.: Science, 1998; 281, 1312-1316.
Go to original source...
Go to PubMed...
- Ethell, D. W., Buhler, L. A.: Clin. Immunol., 2003; 23 (6), 439-446.
Go to original source...
Go to PubMed...
- Charlot, J. F., Prétet, J. L., Haughey, C., Mougin, C.: Apoptosis, 2004; 9, 333-343.
Go to original source...
Go to PubMed...
- Costantini, P., Jacotot, E., Decaudin, D., Kroemer, G. J.: Natl. Cancer Inst., 2000; 92, 1042-1053.
Go to original source...
Go to PubMed...
- Cryns, V., Yuan, J.: Genes Dev., 1998; 12, 1551-1570.
Go to original source...
Go to PubMed...
- Hückelhoven, R.: Apoptosis, 2004; 9, 299-307.
Go to original source...
Go to PubMed...
- Holcik, M., Korneluk, R. G.: Nat. Rev. Mol. Cell Biol., 2001; 7, 550-556.
Go to original source...
Go to PubMed...
- Knudson, C. M., Johnson, G. M., Lin, Y., Korsmeyer, S. J.: Cancer Res., 2001; 61, 659-665.
- Krueger, A., Baumann, S., Krammer, P. H., Kirchhoff, S.: Mol. Cell Biol., 2001; 21 (24), 8247-8254.
Go to original source...
Go to PubMed...
- Alberts, B., Bray, D., Johnson, A. et al.: In: Základy buněčné biologie. Úvod do molekulární biologie buňky. Ústí nad Labem, Espero Publishing, 1998, s. 547-590.
- Nead, M. A., Baglia, L. A., Antinore, M. J. et al.: EMBO J., 1998; 17, 2342-2352.
- Juan, G., Darzynkiewicz, Z.: In: Cell Biology (Celis, J. E., ed.) Academic Press, 1998, s. 261-274.
- Ojo-Amaize, E. A., Nchekwube, E. J., Cottam, H. B. et al.: Cancer Res., 2002; 62, 4007- 4014.
- Gunaratnam, M., Grant, M. H.: Toxicol. in Vitro, 2004; 18 (3), 245-253.
Go to original source...
Go to PubMed...
- http://helios.mol.uj.edu.pl/conf_c/chapters/chap_6.htm
- Steinmetz, M. O., Stoffler, D., Müller, S. A. et al.: J. Mol. Biol., 1998; 276, 1-6.
Go to original source...
Go to PubMed...
- Wary, K. K., Maniero, F., Isakoff, S. J. et al.: Cell, 1996; 87 (4), 733-742.
Go to original source...
Go to PubMed...