title: Cytotoxicity and cellular accumulation of palladium(II) complexes of tetracyclines.
abstract: We studied the cytotoxic effect and the uptake of Pd(II) complexes of doxycycline (Dox), [Pd(Dox)Cl2], and tetracycline (Tc), [Pd(Tc)Cl2], in chronic myelogenous leukemia cells. The effect of the compounds on macrophage viability was also investigated. Compound 1 is more effective than compound 2 in inhibiting the growth of K562 cells with the IC(50) values of 14.44 and 34.54 microM, respectively. There is a good correlation between cell-growth inhibition and intracellular metal concentrations, determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Incubation of the cells with equitoxic concentrations of both compounds yields approximately the same intracellular Pd concentration. At the IC(50) doses, intracellular concentration is ca. 33 x 10(-16) mol/cell for both compounds 1 and 2. This suggests that more [Pd(Tc)Cl2] is needed to produce a cytotoxic effect, because it enters cells more slowly. Both compounds up to 16 microM did not affect the viability of mouse peritoneal macrophages after a 48-h incubation. After 72 h of incubation, the IC(50) values are 22 for [Pd(Dox)Cl2] and 40 microM for [Pd(Tc)Cl(2)]. Therefore, the cytotoxic effect in cancer cells exhibited by both compounds is higher than their effect in macrophages.
authors.affiliation: Department of Chemistry, Universidade Federal de Minas Gerais, Brazil, Avenida Antônio Carlos, 6627, 31.270-901, Belo Horizonte MG, Brazil, (phone: +55 31 34095755; fax: +55 31 34095700).
authors.forename: Flávia C S
authors.initials: FCS
authors.lastname: de Paula
authors.affiliation: Department of Chemistry, Universidade Federal de Minas Gerais, Brazil, Avenida Antônio Carlos, 6627, 31.270-901, Belo Horizonte MG, Brazil, (phone: +55 31 34095755; fax: +55 31 34095700).
authors.forename: Wendell
authors.initials: W
authors.lastname: Guerra
authors.affiliation: Department of Chemistry, Universidade Federal de Minas Gerais, Brazil, Avenida Antônio Carlos, 6627, 31.270-901, Belo Horizonte MG, Brazil, (phone: +55 31 34095755; fax: +55 31 34095700).
authors.forename: Iara R
authors.initials: IR
authors.lastname: Silva
authors.affiliation: Department of Clinical and Toxicological Analyses, Universidade Federal de Minas Gerais, Brazil, Avenida Antônio Carlos, 6627, 31.270-901, Belo Horizonte MG, Brazil.
authors.forename: Josianne N
authors.initials: JN
authors.lastname: Silveira
authors.affiliation: Department of Biochemistry and Imunology, Universidade Federal de Minas Gerais, Brazil, Avenida Antônio Carlos, 6627, 31.270-901, Belo Horizonte MG, Brazil.
authors.forename: Françoise Vasconcelos
authors.initials: FV
authors.lastname: Botelho
authors.affiliation: Department of Biochemistry and Imunology, Universidade Federal de Minas Gerais, Brazil, Avenida Antônio Carlos, 6627, 31.270-901, Belo Horizonte MG, Brazil.
authors.forename: Leda Q
authors.initials: LQ
authors.lastname: Vieira
authors.affiliation: Department of Chemistry, Universidade Federal de Minas Gerais, Brazil, Avenida Antônio Carlos, 6627, 31.270-901, Belo Horizonte MG, Brazil, (phone: +55 31 34095755; fax: +55 31 34095700).
authors.forename: Elene C
authors.initials: EC
authors.lastname: Pereira-Maia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010165:Palladium / Q000737:chemistry*; D013754:Tetracyclines / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D013754:Tetracyclines; D010165:Palladium