Cytotoxicity and cellular accumulation of palladium(II) complexes of tetracyclines.
Chem Biodivers
; 5(10): 2124-2130, 2008 Oct.
Article
de En
| MEDLINE
| ID: mdl-18972502
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Composés organométalliques
/
Palladium
/
Tétracyclines
/
Antinéoplasiques
Limites:
Animals
/
Female
/
Humans
/
Male
Langue:
En
Journal:
Chem Biodivers
Sujet du journal:
BIOQUIMICA
/
QUIMICA
Année:
2008
Type de document:
Article