α5-nAChR/ADAM10 signaling mediates nicotine-related cutaneous melanoma progression via STAT3 activation.

Skin cutaneous melanoma (SKCM) is the skin malignancy with the highest mortality rate, and its morbidity rate is on the rise worldwide. Smoking is an independent marker of poor prognosis in melanoma. The α5-nicotinic acetylcholine receptor (α5-nAChR), one of the receptors for nicotine, is involved in the proliferation, migration and invasion of SKCM cells. Nicotine has been reported to promote the expression of a disintegrin and metalloproteinase 10 (ADAM10), which is the key gene involved in melanoma progression. Here, we explored the link between α5-nAChR and ADAM10 in nicotine-associated cutaneous melanoma. α5-nAChR expression was correlated with ADAM10 expression and lower survival in SKCM. α5-nAChR mediated nicotine-induced ADAM10 expression via STAT3. The α5-nAChR/ADAM10 signaling axis was involved in the stemness and migration of SKCM cells. Furthermore, α5-nAChR expression was associated with ADAM10 expression, EMT marker expression and stemness marker expression in nicotine-related mice homograft tissues. These results suggest the role of the α5-nAChR/ADAM10 signaling pathway in nicotine-induced melanoma progression.

Total Glucosides of Paeony Induce Mitochondrial Dysfunction and Apoptosis by Promoting the Degradation of α5-nAChR in Melanoma Cells.

BACKGROUND: Malignant melanoma is the leading cause of skin cancer-related death, with high malignancy and rapid progression. Total glucosides of paeony (TGP) are extracted from the roots of Paeonia Lactiflora Pall and are widely used in the treatment of chronic hepatitis, rheumatoid arthritis, and adjuvant therapy of tumor chemotherapy. METHODS: In the present research, M14 and A375 cells were treated with TGP. CCK8, transwell and western blotting were performed to analyze the effect of TGP on cell function. RESULTS: TGP treatment impeded the proliferation and migration and activated the apoptosis pathway in melanoma cells. Importantly, TGP induced the degradation of α5-nAChR. Overexpression of α5-nAChR inhibited the anti-cancer effect of TGP. In addition, TGP treatment released cytochrome c from mitochondria into the cytoplasm, inducing mitochondrial dysfunction in melanoma cells. TGP also inhibited the phosphorylation of P38-MAPK, and P38-MAPK inhibitor reduced the promoting effect of α5-nAChR in cell proliferation and migration. CONCLUSION: TGP inhibited cell viability and migration and induced mitochondrial dysfunction and apoptosis by promoting the degradation of α5-nAChR in melanoma cells. This research provided a potential therapeutic anti-cancer drug for treatment strategies of melanoma.

Atomically Dispersed Nickel Anchored on a Nitrogen-Doped Carbon/TiO2 Composite for Efficient and Selective Photocatalytic CH4 Oxidation to Oxygenates.

Direct photocatalytic oxidation of methane to liquid oxygenated products is a sustainable strategy for methane valorization at room temperature. However, in this reaction, noble metals are generally needed to function as cocatalysts for obtaining adequate activity and selectivity. Here, we report atomically dispersed nickel anchored on a nitrogen-doped carbon/TiO2 composite (Ni-NC/TiO2 ) as a highly active and selective catalyst for photooxidation of CH4 to C1 oxygenates with O2 as the only oxidant. Ni-NC/TiO2 exhibits a yield of C1 oxygenates of 198 µmol for 4 h with a selectivity of 93 %, exceeding that of most reported high-performance photocatalysts. Experimental and theoretical investigations suggest that the single-atom Ni-NC sites not only enhance the transfer of photogenerated electrons from TiO2 to isolated Ni atoms but also dominantly facilitate the activation of O2 to form the key intermediate ⋅OOH radicals, which synergistically lead to a substantial enhancement in both activity and selectivity.

Abnormal overexpression of G9a in melanoma cells promotes cancer progression via upregulation of the Notch1 signaling pathway.

Malignant melanoma is a type of very dangerous skin cancer. Histone modifiers usually become dysregulated during the process of carcinoma development, thus there is potential for a histone modifier inhibitor as a useful drug for cancer therapy. There is a multitude of evidence regarding the role of G9a, a histone methyltransferase (HMTase), in tumorigenesis. In this study, we first showed that G9a was significantly upregulated in melanoma patients. Using the TCGA database, we found a significantly higher expression of G9a in primary melanoma samples (n = 461) compared to normal skin samples (n = 551). Next, we knocked down G9a in human M14 and A375 melanoma cell lines in vitro via small interfering RNA (siRNA). This resulted in a significant decrease in cell viability, migration and invasion, and an increase in cell apoptosis. UNC0642 is a small molecule inhibitor of G9a that demonstrates minimal cell toxicity and good in vivo pharmacokinetic characteristics. We investigated the role of UNC0642 in melanoma cells, and detected its anti-cancer effects in vitro and in vivo. Next, we treated cells with UNC0642, and observed a significant decrease in cell viability in M14 and A375 cell lines. Furthermore, treatment with UNC0642 resulted in increased apoptosis. In immunocompetent mice bearing A375 engrafts, treatment with UNC0642 inhibited tumor growth. Results of Western blot analysis revealed that administration of UNC0642 or silencing of G9a expression by siRNA reduced Notch1 expression significantly and decreased the level of Hes1 in A375. All in all, the data from our study demonstrates potential of G9a as a therapeutic target in the treatment of melanoma.

α5-nAChR modulates melanoma growth through the Notch1 signaling pathway.

The roles of α5-nicotinic acetylcholine receptors (α5-nAChRs) in various types of solid cancer have been reported; however, its role in melanoma remains unknown. We knocked down α5-nAChR expression in melanoma cells to investigate the role of α5-nAChR in the proliferation, migration, and invasion of melanoma cells, and its effect on downstream signaling pathways. Using immunohistochemical analysis, we determined that α5-nAChR expression is significantly increased in human melanoma tissues and cell lines compared with normal human skin tissues. Knocking down α5-nAChR expression in melanoma cells in culture significantly inhibited the proliferation, migration, and invasiveness of melanoma cell lines. Specifically, knockdown of α5-nAChR inhibited PI3K-AKT and ERK1/2 signaling activity. Moreover, we confirmed that the Notch1 signaling pathway is the downstream target of α5-nAChR in melanoma. Our findings suggest that α5-nAChR plays a critical role in melanoma development and progression, and that targeting α5-nAChR may be a strategy for melanoma treatment.

Highly Selective Production of Ethylene by the Electroreduction of Carbon Monoxide.

Conversion of carbon monoxide to high value-added ethylene with high selectivity by traditional syngas conversion process is challenging because of the limitation of Anderson-Schulz-Flory distribution. Herein we report a direct electrocatalytic process for highly selective ethylene production from CO reduction with water over Cu catalysts at room temperature and ambient pressure. An unprecedented 52.7 % Faradaic efficiency of ethylene formation is achieved through optimization of cathode structure to facilitate CO diffusion at the surface of the electrode and Cu catalysts to enhance the C-C bond coupling. The highly selective ethylene production is almost without other carbon-based byproducts (e.g. C1 -C4 hydrocarbons and CO2 ) and avoids the drawbacks of the traditional Fischer-Tropsch process that always delivers undesired products. This study provides a new and promising strategy for highly selective production of ethylene from the abundant industrial CO.

Selective light absorber-assisted single nickel atom catalysts for ambient sunlight-driven CO2 methanation.

Ambient sunlight-driven CO2 methanation cannot be realized due to the temperature being less than 80 °C upon irradiation with dispersed solar energy. In this work, a selective light absorber was used to construct a photothermal system to generate a high temperature (up to 288 °C) under weak solar irradiation (1 kW m-2), and this temperature is three times higher than that in traditional photothermal catalysis systems. Moreover, ultrathin amorphous Y2O3 nanosheets with confined single nickel atoms (SA Ni/Y2O3) were synthesized, and they exhibited superior CO2 methanation activity. As a result, 80% CO2 conversion efficiency and a CH4 production rate of 7.5 L m-2 h-1 were achieved through SA Ni/Y2O3 under solar irradiation (from 0.52 to 0.7 kW m-2) when assisted by a selective light absorber, demonstrating that this system can serve as a platform for directly harnessing dispersed solar energy to convert CO2 to valuable chemicals.

Lyn Kinase Promotes the Proliferation of Malignant Melanoma Cells through Inhibition of Apoptosis and Autophagy via the PI3K/Akt Signaling Pathway.

Melanoma is a malignant tumor of cutaneous melanocytes that is characterized by high grade malignancy, rapid progression and high mortality. Thus far, its specific etiological mechanism has been unclear. In this study, we discovered that Lyn kinase expression was up-regulated in melanoma tissues and cells. The function of Lyn was determined by knocking down its expression with a lentivirus containing Lyn shRNA and upregulating its expression with pcDNA3.1-Lyn in the melanoma cell lines M14 and A375. The results showed that Lyn knockdown could significantly inhibit the proliferation, migration and invasiveness through its inhibition of apoptosis and autophagy via the PI3K/Akt pathway in melanoma cell lines. This was further confirmed by treatment with PI3K inhibitor BEZ235. Up-regulation of Lyn promoted the expression of p-Akt and Cyclin D1. Additionally, we investigated the effects of Lyn inhibitor Bafetinib on melanoma cells and the results were consistent with Lyn knockdown. Collectively, our results indicated that Lyn plays a carcinogenic role in multiple cellular functions during melanoma development through regulating apoptosis and autophagy via the PI3K/Akt pathway and may be a valuable potential target for the clinical treatment of melanoma.

Self assembly and controlled drug release of a nano-laminated graphite carbon nitride/methotrexate complex.

In this study, g-C3N4/methotrexate (g-C3N4/MTX) nanohybrids were obtained via a self assembly method. XRD and TEM demonstrated that bulk g-C3N4 had been stripped into thin nanosheets with size range of 150-250 nm. FTIR investigation indicated that the self assembly of the hybrid was attributed to the hydrogen bond between g-C3N4 nanosheets and MTX molecules. It is confirmed by the UV-vis spectra that the hybrids can achieve a sustained drug release within long period for 70 h. Furthermore, the drug release mechanism was investigated by kinetic models and a first-order relationship was concluded, which indicated that the drug release is a simple diffusion process cohydroxyapatite/methotrexate complexntrolled by gradient drug concentration. Cell viability tests confirmed that g-C3N4 presented excellent biocompatibility and g-C3N4/MTX hybrids had obvious suppression efficiency on MG63 cells which showed a positive correlation to the drug concentration and incubation time.

MDA-19 Suppresses Progression of Melanoma Via Inhibiting the PI3K/Akt Pathway.

OBJECTIVE: To investigate the effect of MDA-19 on progression of melanoma, and explore the relevant mechanism. METHODS: The melanoma cell lines, M14 and UACC257, were treated with different concentrations of MDA-19, then CCK8, clone formation assay, Transwell and flow cytometry assays were performed to examine cell proliferation, migration, invasion and apoptosis, respectively. The expression of apoptosis-related proteins (Bcl-2, Bax and caspase 3 P17), EMT and signaling pathway-related proteins were also detected by Western blot. RESULTS: MDA-19 inhibited melanoma cells in a dose-dependent manner. Compared to the NC group, MDA-19 significantly inhibited cell growth capacity, migration and invasion of M14 and UACC257 cells, and accelerated cell apoptosis in a mitochondrial pathway through regulating Bcl-2/Bax and Caspase 3 in M14 and UACC257 cells. Moreover, MDA-19 was observed to up-regulate the expression of E-cad and down-regulate the expression of N-cad, Vimentin and Slug in melanoma cells in vitro. Furthermore, MDA-19 could inhibit the PI3K/Akt pathway by blocking Akt phosphorylation (p-Akt) and downstream proteins, P70 and Cyclin D1 in M14 and UACC257 cells. CONCLUSION: Our data demonstrate that MDA-19 could inhibit progression of melanoma by suppressing the PI3K/Akt pathway, suggesting that MDA-19 is a potential anti-cancer agent for therapy of melanoma.

Regulator of G protein signaling 4 inhibits human melanoma cells proliferation and invasion through the PI3K/AKT signaling pathway.

Melanoma is a tumor produced by skin melanocytes, which has a high metastatic rate and poor prognosis. So far, plenty of work has been done on melanoma, but mechanisms underlying melanoma development have not been fully elucidated. Here we identified regulator of G protein signaling 4(RGS4) as novel therapeutic target for malignant melanoma and its regulating effect on melanoma. We found that endogenous RGS4 expression was much lower in melanoma tissues and cells. In A375 cell line with low endogenous RGS4 expression, the function of RGS4 was detected by up-regulation its expression with pcDNA3.1-RGS4 and knockdown its expression with siRNA. Our results showed that RGS4 could significantly reduce the proliferation, migration and invasion of melanoma cells. RGS4 is an important regulator for the apoptosis of melanocyte, and the apoptosis rate is significantly decreased in low RGS4 enviroment. RGS4 induced non-activation of PI3K/AKT pathway, resulting in decreased expression of E2F1 and Cyclin D1, thus constraining cell proliferation and invasion. These results were further confirmed in M14 cell lines. Collectively, our findings show that RGS4 plays an important role in multiple cellular functions of melanoma development and is valuable to be a therapeutic target.

Nicotinic acetylcholine receptors and cancer.

Nicotine, the primary addictive constituent of cigarettes, is believed to contribute to cancer promotion and progression through the activation of nicotinic acetylcholine receptors (nAChRs), which are membrane ligand-gated cation channels. nAChRs activation can be triggered by the neurotransmitter Ach, or certain other biological compounds, such as nicotine. In recent years, genome-wide association studies have indicated that allelic variation in the α5-α3-ß4 nAChR cluster on chromosome 15q24-15q25.1 is associated with lung cancer risk. The role of nAChRs in other types of cancer has also been reported. The present review highlights the role of nAChRs in types of human cancer.

Surface-Plasmon-Enhanced Photodriven CO2 Reduction Catalyzed by Metal-Organic-Framework-Derived Iron Nanoparticles Encapsulated by Ultrathin Carbon Layers.

Highly efficient utilization of solar light with an excellent reduction capacity is achieved for plasmonic Fe@C nanostructures. By carbon layer coating, the optimized catalyst exhibits enhanced selectivity and stability applied to the solar-driven reduction of CO2 into CO. The surface-plasmon effect of iron particles is proposed to excite CO2 molecules, and thereby facilitates the final reaction activity.

An Amine-Functionalized Iron(III) Metal-Organic Framework as Efficient Visible-Light Photocatalyst for Cr(VI) Reduction.

The photocatalytic reduction of Cr(VI) is investigated over iron(III)-based metal-organic frameworks (MOFs) structured as MIL-88B. It is found that MIL-88B (Fe) MOFs, containing Fe3-µ3-oxo clusters, can be used as photocatalyst for the reduction of Cr(VI) under visible light irradiation, which is due to the direct excitation of Fe3-µ3-oxo clusters. The amine-functionalized MIL-88B (Fe) MOFs (denoted as NH2-MIL-88B (Fe)) shows much higher efficiency for the photocatalytic Cr(VI) reduction under visible-light irradiation compared with MIL-88B (Fe). It is revealed that in addition to the direct excitation of Fe3-µ3-oxo clusters, the amine functionality in NH2-MIL-88B (Fe) can also be excited and then transferred an electron to Fe3-µ3-oxo clusters, which is responsible for the enhanced photocatalytic activity for Cr(VI) reduction. The enhanced photocatalytic activity for Cr(VI) reduction is also achieved for other two amine-functionalized iron(III)-based MOFs (NH2-MIL-53 (Fe) and NH2-MIL-101 (Fe)).