4-Thiazolidinone derivative Les-3833 effectively inhibits viability of human melanoma cells through activating apoptotic mechanisms.

AIM: To evaluate cytotoxic action of 4-thiazolidinone derivative Les-3833 and study the mechanisms of its pro-apoptotic action toward human melanoma cells and human tumor cell lines of other tissue origin. METHODS: The effect of Les-3833 or doxorubicin on the viability of 9 cell lines was studied using MTT assay, while human melanoma cells of WM793 line were additionally examined using light and fluorescent microscopies for evaluating cytomorphological changes. The Western-blot and flow cytometric analyses were carried out to study signaling pathways of melanoma cell cycling and death. RESULTS: Les-3833 was the most efficient against melanoma cells. Its half maximal inhibitory concentration (IC50) was 0.22 µg/mL for WM793 cells and 0.3 µg/mL for SK-Mel-28 melanoma cells. For human lung A549, breast MCF-7, colon HCT116, and ovarian SKOV3 carcinoma cell lines IC50 was in between 2.5 to >5.0 µg/mL. Les-3833 was relatively not toxic (IC50 > 5 µg/mL) for human embryonic kidney HEK293 cells. Results of Annexin V/PI staining of melanoma cells and activation of caspase 3, PARP, MAPK, and EndoG protein suggest apoptosis in Les-3833-treated cells. Les-3833 also induced ROS production in melanoma cells and their arrest in G0/G1 phase of cell cycle. CONCLUSION: Novel 4-thiazolidinone derivative Les-3833 is effective against human melanoma cells in vitro, and such effect is tumor specific since it is much less pronounced in human carcinoma and leukemia cells. In melanoma cells Les-3833 induces apoptosis (morphological changes and increased pro-apoptotic proteins), ROS production, and arrest in G0/G1 phase of cell cycle.

Putative anticancer potential of novel 4-thiazolidinone derivatives: cytotoxicity toward rat C6 glioma in vitro and correlation of general toxicity with the balance of free radical oxidation in rats.

AIM: To evaluate the cytotoxic action of 4-thiazolidinone derivatives (ID 3288, ID 3882, and ID 3833) toward rat glioma C6 cells and to compare the effects of these compounds and doxorubicin on the balance of free radical oxidation (FRO) and antioxidant activity (AOA) in the serum of rats. METHODS: Glioma cells were treated with ID 3882, ID 3288, ID 3833, and doxorubicin, and their cytotoxicity was studied using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and Trypan blue exclusion test, light and fluorescent microscopy, and flow cytometric study of cell cycling and apoptosis, including measuring of Annexin V-positive cells. The contents of superoxide radical, hydrogen peroxide, hydroxyl radical, malonic dialdehyde, and hydrogen sulfide were measured in the serum of rats. Enzymatic activity of superoxide dismutase (SOD), catalase (Cat), and glutathione peroxydase (GPO) was determined. RESULTS: Among novel 4-thiazolidinone derivatives, ID 3288 was most toxic toward rat glioma C6 cells, even compared with doxorubicin. All applied derivatives were less active than doxorubicin in inducing reactive oxygen species-related indicators in the serum of rats. A similar effect was observed when enzymatic indicators of AOA processes were measured. While doxorubicin inhibited the activity of SOD, GPO, and Cat, the effects of 4-thiazolidinone derivatives were less prominent. CONCLUSION: Novel 4-thiazolidinone derivatives differ in their antineoplastic action toward rat glioma C6 cells, and ID 3288 possesses the highest activity compared to doxorubicin. Measurement of indicators of FRO and AOA in the serum of rats treated with these compounds showed their lower general toxicity compared with doxorubicin's toxicity.

The use of hydrophilic poly(N,N-dimethylacrylamide) for promoting engulfment of magnetic gamma-Fe2O3 nanoparticles by mammalian cells.

gamma-Fe2O3 nanoparticles obtained by coprecipitation of Fe(II) and Fe(III) chlorides with a base and subsequent oxidation were coated with a shell of hydrophilic biocompatible poly(N,N-dimethylacrylamide) (PDMAAm). Various initiators were attached to the iron oxide surface to enable the use of the "grafting-from" approach for immobilization of PDMAAm. They included 2,2'-azobis(2-methylpropanimidamide) dihydrochloride (AMPA), 2,2'-azobis(N-hydroxy-2-methylpropanimidamide) dihydrochloride (ABHA) and 4-cyano-4-{[1-cyano-3-(N-hydroxycarbamoyl)-1-methylpropyl]azo}pentanoic acid (CCHPA). Engulfment of PDMAAm-coated y-Fe2O3 nanoparticles by murine J774.2 macrophages was investigated. Only some nanoparticles were engulfed by the macrophages. PDMAAm-AMPA-gamma-Fe2O3 and PDMAAm-ABHA-y-Fe2O3 nanoparticles were rapidly engulfed by the cells. In contrast, neat y-Fe2O3 and PDMAAm-CCHPA-gamma-Fe2O3 particles induced formation of transparent vacuoles indicating toxicity of the particles. Thus, PDMAAm-coated AMPA- and ABHA-gamma-Fe2O3 nanoparticles can be recommended as non-toxic labels for mammalian cells.