Ring-substituted 1-hydroxynaphthalene-2-carboxanilides were previously investigated for their antimycobacterial properties. In our study, we have shown their antiproliferative and cell death-inducing effects in cancer cell lines. Cell proliferation and viability were assessed by WST-1 assay and a dye exclusion test, respectively. Cell cycle distribution, phosphatidylserine externalization, levels of reactive oxygen or nitrogen species (RONS), mitochondrial membrane depolarization, and release of cytochrome c were estimated by flow cytometry. Levels of regulatory proteins were determined by Western blotting. Our data suggest that the ability to inhibit the proliferation of THP-1 or MCF-7 cells might be referred to meta- or para-substituted derivatives with electron-withdrawing groups -F, -Br, or -CF3 at anilide moiety. This effect was accompanied by accumulation of cells in G1 phase. Compound 10 also induced apoptosis in THP-1 cells in association with a loss of mitochondrial membrane potential and production of mitochondrial superoxide. Our study provides a new insight into the action of salicylanilide derivatives, hydroxynaphthalene carboxamides, in cancer cells. Thus, their structure merits further investigation as a model moiety of new small-molecule compounds with potential anticancer properties.
- MeSH
- anilidy chemie farmakologie MeSH
- antitumorózní látky chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- buněčný cyklus účinky léků MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- MFC-7 buňky MeSH
- mitochondrie účinky léků metabolismus MeSH
- molekulární struktura MeSH
- naftoly chemie MeSH
- proliferace buněk účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- salicylanilidy chemie farmakologie MeSH
- superoxidy metabolismus MeSH
- THP-1 buňky MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cellular function is modulated by the electric membrane potential controlling intracellular physiology and signal propagation from a motor neuron to a muscle fiber resulting in muscle contraction. Unlike electric fields, magnetic fields are not attenuated by biological materials and penetrate deep into the tissue. We used complex spatiotemporal magnetic fields (17-70 mT) to control intracellular signaling in skeletal muscle cells. By changing different parameters of the alternating magnetic field (amplitude, inversion time, rotation frequency), we induced transient depolarization of cellular membranes leading to i) Na+ influx through voltage-gated sodium channels (VGSC), ii) cytosolic calcium increase, and iii) VGSC- and ryanodine receptor-dependent increase of actin polymerization. The ion fluxes occurred only, when the field was applied and returned to baseline after the field was turned off. The 30-s-activation-cycle could be repeated without any loss of signal intensity. By contrast, static magnetic fields of the same strength exhibited no effect on myotube Ca2+ levels. Mathematical modeling suggested a role for the alternating magnetic field-induced eddy current, which mediates a local change in the membrane potential triggering the activation of VGSC. These findings might pave the way for the use of complex magnetic fields to improve function of skeletal muscles in myopathies.
- MeSH
- aktiny metabolismus MeSH
- biologické modely MeSH
- buněčná membrána fyziologie MeSH
- buněčné linie MeSH
- gating iontového kanálu MeSH
- kosterní svalová vlákna metabolismus MeSH
- magnetické pole MeSH
- membránové potenciály MeSH
- myoblasty cytologie MeSH
- myši MeSH
- polymerizace MeSH
- sodíkové kanálky řízené napětím fyziologie MeSH
- vápník metabolismus MeSH
- vápníková signalizace MeSH
- viabilita buněk MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The influence of spatially modulated high gradient magnetic fields on cellular functions of human THP-1 leukemia cells is studied. We demonstrate that arrays of high-gradient micrometer-sized magnets induce i) cell swelling, ii) prolonged increased ROS production, and iii) inhibit cell proliferation, and iv) elicit apoptosis of THP-1 monocytic leukemia cells in the absence of chemical or biological agents. Mathematical modeling indicates that mechanical stress exerted on the cells by high magnetic gradient forces is responsible for triggering cell swelling and formation of reactive oxygen species followed by apoptosis. We discuss physical aspects of controlling cell functions by focused magnetic gradient forces, i.e. by a noninvasive and nondestructive physical approach.
- MeSH
- apoptóza MeSH
- leukemie metabolismus patologie MeSH
- lidé MeSH
- magnetismus * MeSH
- mechanický stres MeSH
- monocyty metabolismus patologie MeSH
- nádorové buněčné linie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- teoretické modely * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH