Also published as: Abutaha N, Aggarwal N, Ahmed N, Alatrash N, Arora N, Arsenijevic N, Arsenijević N, Bajusz N, Balakrishnan N, Barlow N, Bartalucci N, Benvenisty N, Bhuvanesh N, Bolaji N, Busto N, Calonghi N, Carenini N, Carson N, Castilho N, Chambers N, Chintakuntla N, Chitrapriya N, Cutillas N, Cvjetan N, Davila-Ferreira N, Deepika N, Dehury N, Demaurex N, Demeubayeva N, Demitri N, Doucet N, Dziuba N, Ehmke N, El Jaafari N, Fayad N, Ferrario N, Gabra N, Gajic N, Gallagher N, Gaudu N, Gerasimchuk N, Gligorijević N, Gmelin N, Greene N, Gruaz N, Gürbüz N, Hyka-Nouspikel N, Häfner N, Ikon N, Janković N, Jiang N, Jyotsana N, K N, Kalhor N, Karaoun N, Kolozsvári N, Lane N, Li N, Liu N, Ljubijankić N, Lu N, Macia N, Malviya N, Manepalli N, Mansour N, Menezes N, Metzler-Nolte N, Mignet N, Miklášová N, Milivojevic N, Milivojević N, Mitina N, Mitro N, Mkhwanazi N, Moini N, Montesdeoca N, Moro N, Mouawad N, Mrnjavac N, Nagesh N, Nambigari N, Nayeem N, Omeñaca N, Orsoni N, Ortega N, Pagliaricci N, Pan N, Penumaka N, Pettenuzzo N, Redaschi N, Rodríguez-Fernández N, Rothman N, Rotthowe N, Roy N, Saad N, Sehgal N, Sheahan N, Shukla N, Sinha N, Smith N, Straková N, Swain N, Szemerédi N, Szoboszlai N, T N, Thorne N, Tian N, Todorović N, Tsaulwayo N, Tsoureas N, Tyagi N, Urakova N, Veerababu N, Vicario N, Viola-Villegas N, Voutier N, Vukea N, Walsh N, Wang N, Wiratpruk N, Wu N, Xu N, Zacharopoulos N, Zhu N
The synthesis, characterization, in vitro imaging, and cytotoxic properties of a new folate conjugate of rhenium(I) are reported. The conjugate [FA-PEG-BQAV-Re(CO)3]+ (gamma-4) was screened against an Show more
The synthesis, characterization, in vitro imaging, and cytotoxic properties of a new folate conjugate of rhenium(I) are reported. The conjugate [FA-PEG-BQAV-Re(CO)3]+ (gamma-4) was screened against an adriamycin- and cisplatin-resistant human ovarian cancer cell line (A2780/AD) that overexpresses the folate receptor (FR). Compound gamma-4 was internalized by a folate-receptor-mediated endocytotic pathway, which results in internal accumulation of gamma-4. This was contrasted with a FR-negative Chinese hamster ovary cell line in which no internalization of gamma-4 was observed. gamma-4 was found to be cytotoxic with IC(50) values of 189 and 78 microM at 6 and 24 h, respectively, toward the FR-positive cell line. This is in contrast to the IC(50) value of 502 microM at 6 h and 84 microM at 24 h for cisplatin in the same cell line, with a significantly greater toxicity at the earlier time point. The cytotoxicity of gamma-4 as explained by interactions that occur between the rhenium(I) complex moiety and DNA is described. Show less
The aim of this study was to investigate cellular response to several ruthenium(III), chromium(III) and rhodium(III) compounds carrying bidentate beta-diketonato ligands: [(acac)--acetylacetonate liga Show more
The aim of this study was to investigate cellular response to several ruthenium(III), chromium(III) and rhodium(III) compounds carrying bidentate beta-diketonato ligands: [(acac)--acetylacetonate ligand, (tfac)--trifluoroacetylacetonate ligand]. Cell sensitivity studies were performed on several cell lines (A2780, cisplatin-sensitive and -resistant U2-OS and U2-OS/Pt, HeLa, B16) using growth-inhibition assay. Effect of intracellular GSH depletion on cell sensitivity to the agents was analyzed in A2780 cells. Flow cytometry was used to assess apoptosis by Annexin-V-FITC/PI staining, and to analyze induction of caspase-3 activity. Possible DNA binding/damaging affinity was investigated, by inductively coupled mass spectrometry, and by 14C-thymidine / 3H-uridine incorporation assay. Cell sensitivity studies showed that the pattern of sensitivity to Ru(tfac)3 complex of the two cisplatin-sensitive/-resistant osteosarcoma cell lines, U2-OS and U2-OS/Pt, was similar to that of A2780 cells (72 h exposure), with the IC50 being around 40 microM. The growth-inhibitory effect of Ru(acac)3 ranged over 100 microM, while Cr(III) and Rh(III) complexes were completely devoid of antitumor action in vitro. Ru(tfac)3 exhibited strong potential for apoptosis induction on A2780 cells (up to 40%) and caused cell cycle arrest in the S phase as well as decrease of the percent of G1 and G2 cells. Ru(acac)3-induced apoptosis was slightly higher than 10%, whereas activation of caspase-3 in HeLa cells was moderate. DNA binding study revealed that only Cr(acac)3 was capable of binding DNA, while Cr(III) and Ru(III) compounds possess potential to inhibit DNA/RNA synthesis. In conclusion, only Ru(III) complexes showed potential for antitumor action. Show less