Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that regulates cell proliferation, differentiation, apoptosis, angiogenesis, inflammation and immune ...responses. Aberrant STAT3 activation triggers tumor progression through oncogenic gene expression in numerous human cancers, leading to promote tumor malignancy. On the contrary, STAT3 activation in immune cells cause elevation of immunosuppressive factors. Accumulating evidence suggests that the tumor microenvironment closely interacts with the STAT3 signaling pathway. So, targeting STAT3 may improve tumor progression, and anti-cancer immune response. In this review, we summarized the role of STAT3 in cancer and the tumor microenvironment, and present inhibitors of STAT3 signaling cascades. BMB Reports 2019; 52(7): 415-423.
While metal‐mediated self‐assembly is a popular technique to construct discrete nanosized objects, highly symmetric structures, built from one type of ligand at a time, are dominating reported ...systems. The tailored integration of a set of different ligands requires sophisticated approaches to avoid narcissistic separation or formation of statistical mixtures. Here, we demonstrate how the combination of three structure‐guiding effects (metal‐templated macrocyclization, additional bridging ligands and shape‐complementarity) based on Co(III)salphen metal nodes allows for a rational and high‐yielding synthesis of structurally complex, lantern‐shaped cages with up to four differentiable bridges. Three new heteroleptic coordination cages based on dinuclear Co(III)salphen macrocycles were synthesized in a one‐pot reaction approach and fully characterized, including single crystal X‐ray analyses. One cage groups two of the same ligands, another two different ligands around a symmetric Co2‐bis‐salphen ring. In the most complex structure, this ring is unsymmetric, rendering all four connections between the two metal centers distinguishable. While heteroleptic assembly around Pd(II) nodes has been shown to be dynamic, beneficial for cage‐to‐cage transformations, assembly cascades and adaptive systems, the herein introduced cages based on kinetically more inert Co(III)salphen will be advantageous for applications in enzyme‐like catalysis and molecular machinery that require enhanced structural and chemical stability.
Stable, low‐symmetry cages can be assembled by completing the octahedral coordination spheres of dinuclear Co(III)salphen macrocycles with shape‐complementary bis‐pyridyl bridges, starting from labile Co(II) precursors under aerobic conditions.
Coordination polymers (CPs: Zn
L
3
n
(X)
2
n
,
L
=
trans
-1,4-bis(imidazolyl)-2-butene; X
−
= BF
4
−
, ClO
4
−
, NO
3
−
) allow for detection of the 4-nitrophenol (4-NP) oxidation process by ...enhanced electrochemical signals. Electrochemical measurement is a highly sensitive method providing much evidence of chemical reactions on an electrode surface. In the present study, we designed and synthesized, with reference to X-ray diffraction data and by spectroscopic analyses, new 3D coordination structures containing imidazolyl donors and zinc(
ii
). The presence of microcrystals Zn
L
3
n
(BF
4
)
2
n
on the working electrode enhanced the redox signals. Therefore, we propose a simple catalytic process that can explain these results and clarify the influence of anions that constitute CP materials used to improve electrochemical detection applications. The CP materials were characterized by nuclear magnetic resonance (NMR), infrared spectroscopy (IR), thermogravimetric (TG) analyses, single crystal X-ray diffraction (SC-XRD), and electrochemical analyses.
To investigate structural and anionic effects of coordination polymers (CPs) on electrochemical sensors, Zn-CPs were synthesized and used for 4-nitrophenol oxidation sensors.
Gravitational forces can impose physical stresses on the human body as it functions to maintain homeostasis. It has been reported that astronauts exposed to microgravity experience altered biological ...functions and many subsequent studies on the effects of microgravity have therefore been conducted. However, the anticancer mechanisms of simulated microgravity remain unclear. We previously showed that the proliferation of human Hodgkin's lymphoma (HL) cells was inhibited when these cells were cultured in time-averaged simulated microgravity (taSMG). In the present study, we investigated whether taSMG produced an anticancer effect. Exposure of human HL cells to taSMG for 2 days increased their reactive oxygen species (ROS) production and NADPH oxidase family gene expression, while mitochondrial mass, ATPase, ATP synthase, and intracellular ATP levels were decreased. Furthermore, human HL cells exposed to taSMG underwent autophagy via AMPK/Akt/mTOR and MAPK pathway modulation; such autophagy was inhibited by the ROS scavenger N-acetylcysteine (NAC). These results suggest an innovative therapeutic approach to HL that is markedly different from conventional chemotherapy and radiotherapy.
The self‐assembly of ZnII ions with 1,3,5‐tris(isonicotinoyloxyethyl)cyanurate produces new topological (42⋅124)3(43)4 2D metal–organic frameworks (MOFs) with anion‐confining cages. The eclipsed ...assembly of each 2D MOF by π–π stacking of cyanurate moieties (3.352(5) Å) forms 3D MOFs consisting of nanochannels (10.5 Å). Two of the three anions are confined in each peanut‐type cage, resulting in hydrophobicity of the nanochannels. The hydrophobic nanochannel effectively adsorbs a wide range of fused aromatic hydrocarbons (FAHs) as monomers or dimers, rendering it potentially highly useful as an energy‐transfer material.
Slotted into place: The direct inclusion and organization of fused aromatic hydrocarbons (FAHs) within the hydrophobic 1D nanochannels of 3D metal–organic frameworks (MOFs) Zn3L4(CH3CN)6(X)6 (L=1,3,5‐tris(isonicotinoyloxyethyl)cyanurate; X−=BF4− and ClO4−) is reported. Förster resonance energy transfer (FRET) with the nanochannels from one FAH derivative to another is described.
Während die metallvermittelte Selbstassemblierung eine beliebte Methode zur Synthese definierter Nanoobjekte ist, wird die Literatur von hochsymmetrischen Strukturen, aufgebaut aus jeweils einer Art ...von Liganden, dominiert. Die kontrollierte Integration einer Reihe verschiedener Liganden erfordert ausgeklügelte Ansätze, um eine narzisstische Trennung oder die Bildung statistischer Mischungen zu vermeiden. Hier zeigen wir, wie die Kombination von drei strukturleitenden Effekten (metallvermittelte Makrozyklisierung, zusätzliches Anbringen von Brückenliganden und Formkomplementarität) auf der Grundlage von Co(III)salphen‐Metallzentren die rationale Synthese von laternenförmigen Käfigen mit bis zu vier differenzierbaren Brücken ermöglicht. Drei neue heteroleptische Koordinationskäfige, basierend auf zweikernigen Co(III)salphen‐Makrozyklen, wurden in einer Eintopfreaktion synthetisiert und vollständig charakterisiert, einschließlich Einkristall‐Röntgenstrukturanalysen. Einer der Käfige gruppiert zwei gleiche Liganden, ein anderer zwei verschiedene Liganden um einen symmetrischen Co2‐Bis‐Salphen‐Ring. In der komplexesten Struktur ist dieser Ring unsymmetrisch, so dass alle vier Brücken zwischen den beiden Metallzentren unterscheidbar sind. Während sich heteroleptische Assemblies mit Pd(II)‐Zentren als dynamisch und vorteilhaft für Käfig‐zu‐Käfig‐Umwandlungen und adaptive Systeme erwiesen haben, werden die hier vorgestellten Käfige auf der Grundlage der kinetisch stabileren Co(III)‐Salphen Einheiten für Anwendungen, die eine erhöhte strukturelle und chemische Stabilität erfordern, von Vorteil sein, z.B. in der enzymähnlichen Katalyse und in molekularen Maschinen.
Stabile Käfige mit niedriger Symmetrie können durch Vervollständigung der oktaedrischen Koordinationsumgebungen von zweikernigen Co(III)salphen‐Makrozyklen mit formkomplementären Bis‐Pyridin‐Brücken ausgehend von labilen Co(II)‐Vorläufern unter aeroben Bedingungen assembliert werden.
Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that regulates cell proliferation, differentiation, apoptosis, angiogenesis, inflammation and immune ...responses. Aberrant STAT3 activation triggers tumor progression through oncogenic gene expression in numerous human cancers, leading to promote tumor malignancy. On the contrary, STAT3 activation in immune cells cause elevation of immunosuppressive factors. Accumulating evidence suggests that the tumor microenvironment closely interacts with the STAT3 signaling pathway. So, targeting STAT3 may improve tumor progression, and anti-cancer immune response. In this review, we summarized the role of STAT3 in cancer and the tumor microenvironment, and present inhibitors of STAT3 signaling cascades. BMB Reports 2019; 52(7): 415-423
Constitutively activated STAT3 plays an essential role in the initiation, progression, maintenance, malignancy, and drug resistance of cancer, including glioblastoma, suggesting that STAT3 is a ...potential therapeutic target for cancer therapy. We recently identified ODZ10117 as a small molecule inhibitor of STAT3 and suggested that it may have an effective therapeutic utility for the STAT3-targeted cancer therapy. Here, we demonstrated the therapeutic efficacy of ODZ10117 in glioblastoma by targeting STAT3. ODZ10117 inhibited migration and invasion and induced apoptotic cell death by targeting STAT3 in glioblastoma cells and patient-derived primary glioblastoma cells. In addition, ODZ10117 suppressed stem cell properties in glioma stem cells (GSCs). Finally, the administration of ODZ10117 showed significant therapeutic efficacy in mouse xenograft models of GSCs and glioblastoma cells. Collectively, ODZ10117 is a promising therapeutic candidate for glioblastoma by targeting STAT3.
PDF
