Intensive investigation for novel antiproliferative and cytotoxic effective chemical compounds is currently concentrated on structurally modified agents of natural or synthetic source. The selenium derivative of triorganotin compound, triphenyltin isoselenocyanate (TPT-NCSe) caused higher cytotoxicity in hormone sensitive MCF 7 (IC 50-250 nM) in comparison with triple-negative MDA-MB-231 breast carcinoma cell line (IC 50-450 nM) as determined by MTT assay. Measurement of DNA damage showed presence of crosslinks in both cell lines treated by increasing TPT-NCSe concentrations. This compound decreased mitochondrial membrane potential shown by JC-1 staining in a concentration-dependent manner in both cell lines. Activation of caspases-3/7 was observed in MDA-MB-231 cells and was significant only by concentrations causing significant level of crosslinks. On the other hand, migration assay revealed inhibitory effect of viability keeping 100 nM concentration of TPT-NCSe on migration of MDA-MB-231 cells. Our data has shown that this selenium containing triorganotin molecule exerts DNA damage-linked antineoplastic activity in breast carcinoma cell lines studied.
- MeSH
- apoptóza MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- nádorové buněčné linie MeSH
- nádory prsu * farmakoterapie MeSH
- organocínové sloučeniny MeSH
- organoselenové sloučeniny MeSH
- proliferace buněk MeSH
- protinádorové látky * chemie farmakologie MeSH
- selen * farmakologie MeSH
- triple-negativní karcinom prsu * metabolismus MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND/AIM: Triple-negative breast cancer (TNBC) constitutes 15-20% of all breast carcinomas, affecting younger women more often and has a worse prognosis than other types of breast cancer, due to the combination of more aggressive clinical behavior and lack of molecular targets for therapy. This study assessed the effects of non-genotoxic concentrations of tributyltin isothiocyanate (TBT-ITC) and triphenyltin isothiocyanate (TPT-ITC) on MDA-MB-231 cells. MATERIALS AND METHODS: MTT assay, comet assay, kinetic imaging and flow cytometry were used for analysis of MDA-MB-231 cells. RESULTS: The results showed that 100 nM concentration of TBT-ITC and TPT-ITC, that did not affect viability or DNA integrity, slowed-down migration by CD44 down-regulation. Moreover, both compounds demonstrated immunomodulatory properties, attenuating PD-L1 expression in MDA-MB-231 cells. CONCLUSION: TPT-ITC was more effective in down-regulating CD44 expression and reducing migration than TBT-ITC, while TBT-ITC was more potent in lowering PD-L1 expression in comparison with TPT-ITC.
- MeSH
- apoptóza účinky léků MeSH
- imunofenotypizace MeSH
- isothiokyanatany chemie farmakologie MeSH
- lidé MeSH
- nádorové biomarkery * MeSH
- nádorové buněčné linie MeSH
- organocínové sloučeniny chemie MeSH
- pohyb buněk účinky léků MeSH
- poškození DNA účinky léků MeSH
- proliferace buněk účinky léků MeSH
- protinádorové látky chemie farmakologie MeSH
- triple-negativní karcinom prsu metabolismus MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
The cytotoxicity of two recently synthesized triorganotin isothiocyanate derivatives, nuclear retinoid X receptor ligands, was tested and compared in estrogen-receptor-positive MCF 7 and -negative MDA-MB-231 human breast carcinoma cell lines. A 48 h MTT assay indicated that tributyltin isothiocyanate (TBT-ITC) is more cytotoxic than triphenyltin isothiocyanate (TPT-ITC) in MCF 7 cells, and the same trend was observed in the MDA-MB-231 cell line. A comet assay revealed the presence of both crosslinks and increasing DNA damage levels after the 17 h treatment with both derivatives. Differences in cytotoxicity of TBT-ITC and TPT-ITC detected by FDA staining correspond to the MTT data, communicating more pronounced effects in MCF 7 than in the MDA-MB-231 cell line. Both derivatives were found to cause apoptosis, as shown by the mitochondrial membrane potential (MMP) depolarization and caspase-3/7 activation. The onset of caspase activation correlated with MMP dissipation and the total cytotoxicity more than with the amount of active caspases. In conclusion, our data suggest that the DNA damage induced by TBT-ITC and TPT-ITC treatment could underlie their cytotoxicity in the cell lines studied.
- MeSH
- apoptóza účinky léků MeSH
- isothiokyanatany chemie farmakologie MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- MFC-7 buňky MeSH
- nádorové buněčné linie MeSH
- nádory prsu farmakoterapie genetika metabolismus MeSH
- organocínové sloučeniny chemie farmakologie MeSH
- poškození DNA účinky léků MeSH
- protinádorové látky chemie farmakologie MeSH
- retinoidní X receptory metabolismus MeSH
- trialkylcínové sloučeniny chemie farmakologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Publikační typ
- abstrakt z konference MeSH
Východisko: Prevalencia hypertenzie a jej determinanty nie sú na Slovensku v populácii adolescentov systematicky sledované. V predloženej práci prezentujeme výsledky sledovania vplyvu vybraných rizikových faktorov životného štýlu (nadhmotnosti, obe - zity, nedostatočnej športovej aktivity, nadmerného času tráveného sedavými činnosťami, solenia, konzumácie jedál, potravín a po - chutín s vysokým obsahom soli, fajčenia) na výšku tlaku krvi u stredoškolskej mládeže. Našim cieľom bolo určiť determinanty pre - hypertenzie a hypertenzie u študentov stredných škôl Bratislavského kraja. Súbor a metódy: Sledovaný súbor tvorilo 4 242 zdravých adolescentov (z toho 48 % chlapcov a 52 % dievčat) vo veku 15–19 ro - kov, ktorí sa v období od novembra 2011 do decembra 2012 zúčastnili projektu Rešpekt pre zdravie. Účasť bola podmienená in - formovaným súhlasom od rodičov. U študentov sme vykonali štandardné merania tlaku krvi a antropometrických parametrov. Vy - brané faktory správania sme zisťovali pomocou anonymného dotazníka. Na sledovanie vzťahov medzi premennými sme použili viacrozmernú logistickú regresiu. Modely sme adjustovali na vek a pohlavie. Výsledky: Šanca mať prehypertenziu a hypertenziu bola signifikantne vyššia u študentov s nadváhou (p < 0,001; p < 0,001), obe - zitou (p < 0,001; p < 0,001) a u tých, ktorí počas pracovného týždňa trávili v rámci svojho voľného času viac ako dve hodiny den - ne pri obrazovke počítača a/alebo televízora (p = 0,007; p = 0,001). Záver : Ukázalo sa, že nadváha, obezita a množstvo času stráveného pri počítači a/alebo televízore u adolescentov významným spôsobom ovplyvňujú tlak krvi. Je dôležité, aby sa s ich prevenciou začalo už v ranom veku, kedy si deti utvárajú zvyčajne celoži - votné návyky.
Background: In Slovakia, prevalence of hypertension and its determinants in the population of adolescents have not been syste - matically monitored. In this study we present the results of observing the impacts of selected risk factors of lifestyle (overweight, obesity, physical inactivity, excessive time spent over sedentary activities, salting, consumption of food with high salt content, smo - king) on blood pressure in high school youth. Our goal has been to define the determinants of prehypertension and hypertension in students of Bratislava district, high schools in. Population and methods: The targeted group was composed of 4,242 healthy adolescents (48% boys and 52% girls) at the age of 15–19 who had participated in the project Respect for health between November 2011 and December 2012. Participation in the project was conditioned by an informed consent of their parents. In standard fashion, we measured their blood pressure and anthro - pometric parameters. We had been detecting chosen factors of behavior via an anonymous questionnaire. Subsequently, multino - mial logistic regression has been applied to monitor the relations between the variables. We adjusted the models to age and gender. Results: The odds of prehypertension and hypertension were significantly higher among the students with overweight (p < 0.001; p < 0.001), obesity (p < 0.001; p < 0.001) and those who spend, during a workweek in the scope of their spare time, more than two hours daily at the screen of their computers or TV's. (p = 0.007; p = 0.001). Conclusion: It has been proven that overweight, obesity and a great amount of time spent on the computer and/or TV in the ado - lescents has a significant impact on blood pressure. It is important to commence the prevention of these risky factors at the early age of children since children establish their lifelong customs at that stage of their life.
- MeSH
- hypertenze * MeSH
- kouření škodlivé účinky MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nadváha MeSH
- prehypertenze MeSH
- rizikové faktory * MeSH
- volnočasové aktivity MeSH
- zdravý životní styl MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Geografické názvy
- Slovenská republika MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
The genotoxic potential of extractable organic matter (EOM) associated with the respirable particulate matter (PM <10 microm) of atmospheric pollution has been determined in three European cities--Prague (Czech Republic, two monitoring sites, Libus and Smíchov), Kosice (Slovak Republic) and Sofia (Bulgaria) using the alkaline single-cell gel electrophoresis (the comet assay). The EOM samples were extracted by dichloromethane from ambient airborne particles collected daily (24 h intervals) during 3-month sampling periods in winter and summer seasons. The human metabolically competent cell line Hep G2 was used as a test system and benzo[a]pyrene (BaP), a known carcinogen, was applied as a positive control (internal standard) in each electrophoretic run. Two-hour exposure of Hep G2 cells to equivalent EOM concentrations ranging from 5 to 150 microg EOM/ml resulted in a linear dose-dependent increase of DNA migration (r > 0.9, P < 0.01). A less significant dose-response (r = 0.61) was only induced by the EOM sample from the locality Prague-Libus (PRG-LB) in the winter. Generally, a 1.5 to four-fold increase of DNA strand breaks over the background control level was determined in EOM-exposed cells. In order to compare the genotoxic potential of individual EOMs, a mathematical model was used to correct the 'real' data. No substantial location- or season-related differences were found in EOM genotoxicity (EOM microg/ml), except for the EOM sample from Sofia, collected in the summer. This EOM sample induced a nearly two-fold lower level of DNA damage in comparison with other EOMs. On the other hand, clear statistically significant location- and season-related differences (P < 0.001) in ambient air genotoxicity were determined when the EOM quantity per cubic meter of air (microg/m3) was taken into account. In that case, the genotoxicity of winter air pollution was six- to 10-fold higher in comparison with summer air. The air pollution genotoxicity in individual localities rose during the winter season in the order: PRG-LB < Kosice < Prague-Smíchov (PRG-SM) < Sofia, while during the summer season the highest ambient air genotoxicity was revealed in the locality Prague-Smíchov and approximately equal air pollution genotoxicity was determined among localities Prague-Libus, Kosice and Sofia (PRG-LB approximately Kosice approximately Sofia < PRG-SM). The greatest overall air pollution genotoxicity was determined in the locality Sofia during the winter season. In a time course study to evaluate the kinetics of DNA strand break rejoining it was shown that the level of DNA strand breaks in EOM-exposed cells has returned to near the background level within 24 h after the treatment.
- MeSH
- benzopyren toxicita MeSH
- DNA účinky léků MeSH
- karcinogeny toxicita MeSH
- kometový test MeSH
- látky znečišťující vzduch toxicita MeSH
- lidé MeSH
- mutageny toxicita MeSH
- nádorové buněčné linie MeSH
- oprava DNA MeSH
- organické látky toxicita MeSH
- poškození DNA MeSH
- roční období MeSH
- testy genotoxicity MeSH
- velkoměsta * MeSH
- znečištění ovzduší * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Bulharsko MeSH
- Česká republika MeSH
- Slovenská republika MeSH
- velkoměsta * MeSH
