Application of near-infrared-to-blue upconversion luminescence for the polymerization of resin cements through zirconia discs.

OBJECTIVES: To investigate a near-infrared-to-blue luminescence upconversion curing method for polymerizing resin cements under zirconia discs. METHODS: Lava zirconia discs of different thicknesses (0.5-2.0 mm) were manufactured. First, the transmittances of the NIR and two blue lights (BLs) (LED and halogen lights) through these discs were measured. Second, NaYF4:Yb3+/Tm3+ upconversion phosphor (UP) powder was milled into 0.5-µm particle sizes. A light-curable resin cement VariolinkII base was chosen as the control (UP0), and an experimental cement (UP5) was prepared by adding 5 % UPs. These two cements were examined using multiphoton excitation microscopy for particle distribution. UP5 and UP0 were polymerized with or without zirconia shielding then subjected to a microhardness test. A multifold analysis was performed to examine the effects of zirconia thickness, curing protocols (pure BL or combined BL and NIR curing), and cement type. RESULTS: The transmittance of NIR was superior to that of BL through zirconia discs of all thicknesses. UP particles were homogeneously distributed in UP5 and emitted blue luminescence under 980-nm NIR excitation. UP5 showed higher microhardness values than UP0 under any curing protocol or zirconia shielding condition. The combination of 20-s BL and 40-s NIR curing yielded the highest microhardness in uncovered UP5. However, combining 40-s BL and 20-s NIR curing surpassed the other groups when the zirconia discs were thicker than 0.5 mm. SIGNIFICANCE: NIR exhibits higher transmission through zirconia than BL. UP particles work as strengthen fillers and photosensitizers in cements. NIR upconversion curing could be a new strategy for polymerizing resin cements under thick zirconia restorations.

Phenethyl isothiocyanate and irinotecan synergistically induce cell apoptosis in colon cancer HCT 116 cells in vitro.

Irinotecan (IRI), an anticancer drug to treat colon cancer patients, causes cytotoxic effects on normal cells. Phenethyl isothiocyanate (PEITC), rich in common cruciferous plants, has anticancer activities (induction of cell apoptosis) in many human cancer cells, including colon cancer cells. However, the anticancer effects of IRI combined with PEITC on human colon cancer cells in vitro were unavailable. Herein, the aim of this study is to focus on the apoptotic effects of the combination of IRI and PEITC on human colon cancer HCT 116 cells in vitro. Propidium iodide (PI) exclusion and Annexin V/PI staining assays showed that IRI combined with PEITC decreased viable cell number and induced higher cell apoptosis than that of IRI or PEITC only in HCT 116 cells. Moreover, combined treatment induced higher levels of reactive oxygen species (ROS) and Ca2+ than that of IRI or PEITC only. Cells pre-treated with N-acetyl-l-cysteine (scavenger of ROS) and then treated with IRI, PEITC, or IRI combined with PEITC showed increased viable cell numbers than that of IRI or PEITC only. IRI combined with PEITC increased higher caspase-3, -8, and -9 activities than that of IRI or PEITC only by flow cytometer assay. IRI combined with PEITC induced higher levels of ER stress-, mitochondria-, and caspase-associated proteins than that of IRI or PEITC treatment only in HCT 116 cells. Based on these observations, PEITC potentiates IRI anticancer activity by promoting cell apoptosis in the human colon HCT 116 cells. Thus, PEITC may be a potential enhancer for IRI in humans as an anticolon cancer drug in the future.

Extracranial metastasis of pediatric glioblastoma: case report and literature review.

Glioblastoma (GBM) is a rare primary brain tumor in children, and extracranial metastases of pediatric GBM are particularly uncommon. We present the case of a 10-year-old girl with pediatric GBM who developed multiple extracranial metastases, including cervical lymph nodes, spine, and lung. We discuss the rarity of extracranial metastases in GBM and explore possible mechanisms of dissemination. The patient underwent surgical resections, radiotherapy, and chemotherapy, but the metastatic disease progressed despite treatment. We emphasize the need to consider extracranial metastases in pediatric GBM patients and adopt multimodal treatment approaches for managing this rare clinical entity. As the survival rates of pediatric GBM patients are improving, awareness of extracranial metastases is crucial for optimizing treatment outcomes.

Allyl Isothiocyanate (AITC) Induces Apoptotic Cell Death In Vitro and Exhibits Anti-Tumor Activity in a Human Glioblastoma GBM8401/luc2 Model.

Some clinically used anti-cancer drugs are obtained from natural products. Allyl isothiocyanate (AITC), a plant-derived compound abundant in cruciferous vegetables, has been shown to possess an anti-cancer ability in human cancer cell lines in vitro, including human brain glioma cells. However, the anti-cancer effects of AITC in human glioblastoma (GBM) cells in vivo have not yet been examined. In the present study, we used GBM8401/luc2 human glioblastoma cells and a GBM8401/luc2-cell-bearing animal model to identify the treatment efficacy of AITC. Here, we confirm that AITC reduced total cell viability and induced cell apoptosis in GBM8401/luc2 cells in vitro. Furthermore, Western blotting also showed that AITC induced apoptotic cell death through decreased the anti-apoptotic protein BCL-2, MCL-1 expression, increased the pro-apoptotic protein BAX expression, and promoted the activities of caspase-3, -8, and -9. Therefore, we further investigated the anti-tumor effects of AITC on human GBM8401/luc2 cell xenograft mice. The human glioblastoma GBM8401/luc2 cancer cells were subcutaneously injected into the right flank of BALB/c nude mice to generate glioblastoma xenograft mice. The animals were randomly divided into three groups: group I was treated without AITC (control); group II with 0.1 mg/day of AITC; and group III with 0.2 mg/day of AITC every 3 days for 27 days. Bodyweight, and tumor volume (size) were recorded every 3 days. Tumors exhibiting Luc2 intensity were measured, and we quantified intensity using Living Image software on days 0, 12, and 24. After treatment, tumor weight from each mouse was recorded. Tumor tissues were examined for histopathological changes using H&E staining, and we analyzed the protein levels via immunohistochemical analysis. Our results indicate that AITC significantly inhibited tumor growth at both doses of AITC due to the reduction in tumor size and weight. H&E histopathology analysis of heart, liver, spleen, and kidney samples revealed that AITC did not significantly induce toxicity. Body weight did not show significant changes in any experiment group. AITC significantly downregulated the protein expression levels of MCL-1, XIAP, MMP-9, and VEGF; however, it increased apoptosis-associated proteins, such as cleaved caspase-3, -8, and -9, in the tumor tissues compared with the control group. Based on these observations, AITC exhibits potent anti-cancer activity in the human glioblastoma cell xenograft model via inhibiting tumor cell proliferation and the induction of cell apoptosis. AITC may be a potential anti-GBM cancer drug that could be used in the future.

Phenethyl Isothiocyanate Suppresses the Proinflammatory Cytokines in Human Glioblastoma Cells through the PI3K/Akt/NF-κB Signaling Pathway In Vitro.

Phenethyl isothiocyanate (PEITC), extracted from cruciferous vegetables, showed anticancer activity in many human cancer cells. Our previous studies disclosed the anticancer activity of PEITC in human glioblastoma multiforme (GBM) 8401 cells, including suppressing the cell proliferation, inducing apoptotic cell death, and suppressing cell migration and invasion. Furthermore, PEITC also inhibited the growth of xenograft tumors of human glioblastoma cells. We are the first to investigate PEITC effects on the receptor tyrosine kinase (RTK) signaling pathway and the effects of proinflammatory cytokines on glioblastoma. The cell viability was analyzed by flow cytometric assay. The protein levels and mRNA expressions of cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), were determined by enzyme-linked immunosorbent assay (ELISA) reader and real-time polymerase chain reaction (PCR) analysis, respectively. Furthermore, nuclear factor-kappa B- (NF-κB-) associated proteins were evaluated by western blotting. NF-κB expression and nuclear translocation were confirmed by confocal laser microscopy. NF-κB binding to the DNA was examined by electrophoretic mobility shift assay (EMSA). Our results indicated that PEITC decreased the cell viability and inhibited the protein levels and expressions of IL-1ß, IL-6, and TNF-α genes at the transcriptional level in GBM 8401 cells. PEITC inhibited the binding of NF-κB on promoter site of DNA in GBM 8401 cells. PEITC also altered the protein expressions of protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and NF-κB signaling pathways. The inflammatory responses in human glioblastoma cells may be suppressed by PEITC through the phosphoinositide 3-kinase (PI3K)/Akt/NF-κB signaling pathway. Thus, PEITC may have the potential to be an anti-inflammatory agent for human glioblastoma in the future.

Novel Polymerization of Dental Composites Using Near-Infrared-Induced Internal Upconversion Blue Luminescence.

Blue light (BL) curing on dental resin composites results in gradient polymerization. By incorporating upconversion phosphors (UP) in resin composites, near-infrared (NIR) irradiation may activate internal blue emission and a polymerization reaction. This study was aimed to evaluate the competency of the NIR-to-BL upconversion luminance in polymerizing dental composites and to assess the appropriate UP content and curing protocol. NaYF4 (Yb3+/Tm3+ co-doped) powder exhibiting 476-nm blue emission under 980-nm NIR was adapted and ball-milled for 4-8 h to obtain different particles. The bare particles were assessed for their emission intensities, and also added into a base composite Z100 (3M EPSE) to evaluate their ability in enhancing polymerization under NIR irradiation. Experimental composites were prepared by dispensing the selected powder and Z100 at different ratios (0, 5, 10 wt% UP). These composites were irradiated under different protocols (BL, NIR, or their combinations), and the microhardness at the irradiated surface and different depths were determined. The results showed that unground UP (d50 = 1.9 µm) exhibited the highest luminescence, while the incorporation of 0.4-µm particles obtained the highest microhardness. The combined 20-s BL and 20-120-s NIR significantly increased the microhardness on the surface and internal depths compared to BL correspondents. The 5% UP effectively enhanced the microhardness under 80-s NIR irradiation but was surpassed by 10% UP with longer NIR irradiation. The combined BL-NIR curing could be an effective approach to polymerize dental composites, while the intensity of upconversion luminescence was related to specific UP particle size and content. Incorporation of 5-10% UP facilitates NIR upconversion polymerization on dental composites.

Tetrandrine Suppresses Human Brain Glioblastoma GBM 8401/luc2 Cell-Xenografted Subcutaneous Tumors in Nude Mice In Vivo.

Tetrandrine (TET), a bisbenzylisoquinoline (BBI) alkaloid, is isolated from the plant Stephania tetrandra S. Moore and has a wide range of biological activity, including anticancer properties in vitro and in vivo. At first, we established a luciferase-expressing stable clone that was named GBM 8401/luc2 cells. Herein, the primary results indicated that TET reduced the total cell viability and induced cell apoptosis in GBM 8401/luc2 human glioblastoma cells. However, there is no available information showing that TET suppresses glioblastoma cells in vivo. Thus, we investigated the effects and mechanisms of TET on a GBM 8401/luc2 cell-generated tumor in vivo. After the tumor volume reached 100-120 mm3 in subcutaneously xenografted nude mice, all of the mice were randomly divided into three groups: Group I was treated with phosphate-buffered solution (PBS) containing 0.1% dimethyl sulfoxide, Group II with 25 mg/kg of TET, and Group III with 50 mg/kg of TET. All mice were given the oral treatment of PBS or TET by gavage for 21 days, and the body weight and tumor volumes were recorded every 5 days. After treatment, individual tumors, kidneys, livers, and spleens were isolated from each group. The results showed that TET did not affect the body weights, but it significantly decreased the tumor volumes. The TET treatment at 50 mg/kg had a two-fold decrease in tumor volumes than that at 25 mg/kg when compared to the control. TET decreased the total photon flux, and treatment with TET at 50 mg/kg had a lower total photon flux than that at 25 mg/kg, as measured by a Xenogen IVIS imaging system. Moreover, the higher TET treatment had lower tumor volumes and weights than those of the lower dose. The apoptosis-associated protein expression in the tumor section was examined by immunohistochemical analysis, and the results showed that TET treatment reduced the levels of c-FLIP, MCL-1, and XIAP but increased the signals of cleaved-caspase-3, -8, and -9. Furthermore, the hematoxylin and eosin (H & E) staining of kidney, liver, and spleen tissues showed no significant difference between the TET-treated and control groups. Overall, these observations demonstrated that TET suppressed subcutaneous tumor growth in a nude-mice model via the induction of cell apoptosis.

Ouabain Suppresses Cell Migration and Invasion in Human Gastric Cancer AGS Cells Through the Inhibition of MMP Signaling Pathways.

BACKGROUND/AIM: Ouabain has been shown to induce human cancer cell death via apoptosis. Still, its anti-metastatic effect on cell migration and invasion of human gastric cancer cells has not been addressed. MATERIALS AND METHODS: Cell proliferation and viability were measured by the MTT assay and flow cytometry, respectively. Cell motitlity was analysed by wound healing assay. Cell migration and invasion were analysed by the transwell system. Protein expression was assayed by western blotting. RESULTS: Ouabain decreased AGS cell proliferation, cell viability, and motility. In addition, ouabain inhibited AGS cell migration and invasion. Furthermore, ouabain decreased matrix metalloproteinase-2 (MMP-2) activity at 48 h. Ouabain reduced the levels of proteins associated with PI3K/AKT and p38/MAPK pathways. In addition, ouabain decreased the expressions of N-cadherin, tissue inhibitor of metalloproteinases-1 (TIMP-1), urokinase-type plasminogen activator (c-uPA), and MMP-2 at 48 h. CONCLUSION: Ouabain suppresses cell metastasis through multiple signaling pathways in AGS cells.

Pre-Treatment of Pterostilbene Enhances H2O2-induced Cell Apoptosis Through Caspase-dependent Pathway in Human Keratinocyte Cells.

BACKGROUND/AIM: Hydrogen peroxide (H2O2) is one of the reactive oxygen species (ROS), which can induce apoptotic cell death in numerous cancer cells. Pterostilbene (PTE), a natural polyphenolic compound, induces cell apoptosis in many human cancer cells. MATERIALS AND METHODS: We investigated whether PTE could enhance H2O2-induced cell apoptosis in human keratinocyte HaCaT cells in vitro. The morphological change of HaCaT cells was observed and photographed under a contrast-phase microscope. The percentage of cell viability was measured by propidium iodide exclusion assay. Cell apoptosis was performed by Annexin V/PI double staining and assayed by flow cytometer. DNA condensation was measured by DAPI staining. The protein expression was determined by western blotting. ROS production-associated proteins were also assayed by confocal laser scanning microscopy. RESULTS: PTE pre-treatment enhanced H2O2 (600 µM)-induced cell morphological changes and reduced the total cell number (cell viability). The decreased cell viability in HaCaT cells was through induction of apoptotic cell death, which was confirmed by Annexin V/PI double staining and DAPI staining. Western blotting studies indicated that HaCaT cells which were pre-treated with PTE (100 µM) and then co-treated with H2O2 (600 µM) for 12 h showed significantly increased levels of SOD (Cu/Zn), SOD (Mn), Bax, caspase-3, caspase-8, caspase-9, PARP, p53, p-p53, and p-H2A.X but decreased levels Bcl-2 and catalase. Results also showed that HaCaT cells pre-treated with PTE and then co-treated with H2O2 had increased expression of SOD (Cu/Zn) and glutathione but decreased catalase. CONCLUSION: These observations suggest that PTE pre-treatment can enhance the H2O2-induced apoptotic cell death in keratinocyte cells and may be an effective candidate for the treatment of proliferative keratinocytes.

Genistein enhances the effects of L-asparaginase on inducing cell apoptosis in human leukemia cancer HL-60 cells.

Genistein (GEN) has been shown to induce apoptotic cell death in various human cancer cells. L-asparaginase (Asp), a clinical drug for leukemia, has been shown to induce cell apoptosis in leukemia cells. No available information concerning GEN combined with Asp increased the cell apoptosis compared to GEN or Asp treatment alone. The objective of this study is to evaluate the anti-leukemia activity of GEN combined with Asp on human leukemia HL-60 cells in vitro. The cell viability, the distribution of cell cycle, apoptotic cell death, and the level of ΔΨm were examined by flow cytometric assay. The expressions of apoptosis-associated proteins were measured by western blotting. GEN combined with Asp revealed a more significant decrease in total viable cells and induced a higher percentage of G2/M phase arrest, DNA damage, and cell apoptosis than that of GEN or Asp treatment only in HL-60 cells. Furthermore, the combined treatments (GEN and Asp) showed a higher decrease in the level of ΔΨm than that of GEN or Asp treatment only. These results indicated that GEN combined with Asp induced mitochondria dysfunction by disrupting the mitochondrial membrane potential. The results from western blotting demonstrated that the treatment of GEN combined with Asp showed a higher increase in the levels of Bax and Bak (pro-apoptotic proteins) and an active form of caspase-3 and a higher decrease in Bcl-2 (anti-apoptotic protein) than that of GEN or Asp treatment alone. GEN significantly enhances the efficiency of Asp on cytotoxic effects (the induction of apoptosis) in HL-60 cells.

Demethoxycurcumin Inhibits In Vivo Growth of Xenograft Tumors of Human Cervical Cancer Cells.

BACKGROUND/AIM: Demethoxycurcumin (DMC), a derivate of curcumin from natural plants, exerts antitumor effects on various human cancer cells in vitro and in vivo. Nevertheless, no reports have disclosed whether DMC can affect the growth of human cervical cancer cells in vivo. Therefore we investigated the antitumor effects of DMC on a HeLa cell xenograft model in nude mice in this study. MATERIALS AND METHODS: Twenty-four nude mice were subcutaneously injected with HeLa cells. All mice were randomly divided into control, low-dose DMC (30 mg/kg), and high-dose DMC (50 mg/kg) groups and individual mice were treated intraperitoneally accordingly every 2 days. RESULTS: DMC significantly reduced tumor weights and volumes of HeLa cell xenografts in mice, indicating the suppression of growth of xenograft tumors. CONCLUSION: These effects and findings might provide evidence for investigating the potential use of DMC as an anti-cervical cancer drug in the future.

Tetrandrine inhibits cell migration and invasion in human nasopharyngeal carcinoma NPC-TW 039 cells through inhibiting MAPK and RhoA signaling pathways.

The objective of this study was to investigate the effects of tetrandrine (TET) on cell migration and invasion of nasopharyngeal carcinoma NPC-TW 039 cells in vitro. TET at 1-10 µM did not change cell morphology and also did not decrease the total cell viability and proliferation in NPC-TW 039 cells. It decreased the cell mobility based on decreased wound closure in NPC-TW 039 cells by wound healing assay. TET suppressed the cell migration and invasion using transwell system. TET reduced MMP-2 activities at 1-10 µM and these effects are in dose-dependently. After exposed to various treatments, TET decreased the levels of p-ERK, p-JNK, p-p38, RhoA, and NF-κB at 48 hr. Based on these findings, we may suggest TET-inhibited cell migration and invasion of NPC-TW 039 cells via the suppression of MAPK and RhoA signaling pathways for inhibiting the MMP-2 and -9 expression in vitro. PRACTICAL APPLICATIONS: Tetrandrine (TET), a bis-benzylisoquinoline alkaloid, is obtained from the dried root of Stephania tetrandra. TET has been shown to induce cancer cell apoptosis on human cancer cells but its anti-metastasis effect on cell migration and invasion of nasopharyngeal carcinoma cells has not been investigated. Our results showed that TET significantly repressed the cell mobility, migration, and invasion of NPC-TW 039 cells in vitro that involved in inhibiting RhoA, Ras accompanying with p38/MAPK signaling pathway. We conclude that TET may be the anticancer agents for nasopharyngeal carcinoma therapy in the future.

Chrysin inhibit human melanoma A375.S2 cell migration and invasion via affecting MAPK signaling and NF-κB signaling pathway in vitro.

Numerous evidences have shown that chrysin induced cytotoxic effects via induced cell cycle arrest and induction of cell apoptosis in human cancer cell lines, however, no information showed that chrysin inhibited skin cancer cell migration and invasion. In this study, we investigated anti-metastasis mechanisms of chrysin in human melanoma cancer A375.S2 cells in vitro. Under sub-lethal concentrations of chrysin (0, 5, 10, and 15 µM) which inhibits cell mobility, migration and invasion of A375.S2 cells that were assayed by wound healing and Transwell filter. That chrysin inhibited MMP-2 activity in A375.S2 cells was investigated by gelatin zymography assay. Western blotting was used to examine protein expression and results indicated that chrysin inhibited the expression of GRB2, SOS-1, PKC, p-AKT (Thr308), NF-κBp65, and NF-κBp50 at 24 and 48 hours treatment, but only at 10-15 µM of chrysin decreased Ras, PI3K, p-c-Jun, and Snail only at 48 hours treatment and only decrease p-AKT(Ser473) at 24 hours treatment. Furthermore, chrysin (5-15 µM) decreased the expression of uPA, N-cadherin and MMP-1 at 24 and 48 hours treatment but only decreased MMP-2 and VEGF at 48 hours treatment at 10-15 µM and 5-15 µM of chrysin, respectively, however, increased E-cadherin at 5-15 µM treatment. Results of confocal laser microscopy systems indicated that chrysin inhibited expression of NF-κBp65 in A375.S2 cells. Based on these observations, we suggest that chrysin can be used in anti-metastasis of human melanoma cells in the future.

Benzyl Isothiocyanate Induces Apoptotic Cell Death Through Mitochondria-dependent Pathway in Gefitinib-resistant NCI-H460 Human Lung Cancer Cells In Vitro.

BACKGROUND/AIM: Gefitinib is used to treat patients with lung cancer, but in some patients, the disease becomes gefitinib-resistant. Benzyl isothiocyanate (BITC), found in cruciferous vegetables, has shown anticancer activity in many human cancer cell lines. However, the effects of BITC on gefitinib-resistant NCI-H460 lung cancer cells in vitro have not been investigated. MATERIALS AND METHODS: The effects of BITC on gefitinib-resistant NCI-H460 lung cancer cells were investigated in vitro. Flow cytometric assay was used for determining the total viable cell number, apoptotic cell death, the production of reactive oxygen species (ROS) and Ca2+, mitochondriaI membrane potential (Ψm) and caspase-3, -8 and -9 activities. Furthermore, 4', 6-diamidino-2-phenylindole staining was used to examine chromatin condensation in NCI-H460 and NCI-H460/G cells. RESULTS: BITC reduced total viable cell number via the induction of apoptotic cell death, that was also confirmed by annexin V/propidium iodide double staining assay. BITC increased ROS and Ca2+ production, reduced Ψm and increased caspase-3, -8 and -9 activities in both NCI-H460 and NCI-H460/G cells. Western blotting assay also showed that BITC increased expression of cleaved caspase-3 and -9, cytochrome c, BCL2-associated X protein, endonuclease G, poly (ADP-ribose) polymerase, growth arrest and DNA-damage protein 153, caspase-7 and activating transcription factor 6 alpha, but reduced apoptosis-inducing factor and caspase-9, BH3-interacting domain death agonist, calpain 1, glucose-regulated protein 78 and inositol requiring enzyme 1 alpha in NCI-H460/G cells. CONCLUSION: BITC-induced apoptotic cell death appears to occur via caspase- and mitochondria-dependent pathways in both cell lines.

Phenethyl Isothiocyanate Inhibits In Vivo Growth of Xenograft Tumors of Human Glioblastoma Cells.

Phenethyl isothiocyanate (PEITC) from cruciferous vegetables can inhibit the growth of various human cancer cells. In previous studies, we determined that PEITC inhibited the in vitro growth of human glioblastoma GBM 8401 cells by inducing apoptosis, inhibiting migration and invasion, and altering gene expression. Nevertheless, there are no further in vivo reports disclosing whether PEITC can suppress the growth of glioblastoma. Therefore, in this study we investigate the anti-tumor effects of PEITC in a xenograft model of glioblastoma in nude mice. Thirty nude mice were inoculated subcutaneously with GBM 8401 cells. Mice with one palpable tumor were divided randomly into three groups: control, PEITC-10, and PEITC-20 groups treated with 0.1% dimethyl sulfoxide (DMSO), and 10 and 20 µmole PEITC/100 µL PBS daily by oral gavage, respectively. PEITC significantly decreased tumor weights and volumes of GBM 8401 cells in mice, but did not affect the total body weights of mice. PEITC diminished the levels of anti-apoptotic proteins MCL-1 (myeloid cell leukemia 1) and XIAP (X-linked inhibitor of apoptosis protein) in GBM 8401 cells. PEITC enhanced the levels of caspase-3 and Bax in GBM 8401 cells. The growth of glioblastoma can be suppressed by the biological properties of PEITC in vivo. These effects might support further investigations into the potential use of PEITC as an anticancer drug for glioblastoma.

p-GaN/n-ZnO nanorods: the use of graphene nanosheets composites to increase charge separation in self-powered visible-blind UV photodetectors.

ZnO-based heterojunctions have found applications as self-powered ultraviolet photodetectors (PDs). However, high doping levels are not compatible with high mobility for metallic doped ZnO-based PDs so further development has been inhibited. This study demonstrates a method to increase the open-circuit voltage (V oc) that allows keeping a sufficiently high level of mobility of ZnO, using a ZnO nanorod/GaN heterojunction that incorporates graphene nanosheets as the active layer. These hybrid PDs have triple the value for V oc of PDs that have only pure ZnO and better exhibit photo-response characteristics. The results of surface Kelvin probe microscopy and x-ray photoelectron spectrometer show that the complex defects that occur because Zn interstitials form a shallow donor in ZnO are mainly responsible for the increase in the value of V oc. Using this functional nanostructure as an active layer represents a new method for the manufacture of high-performance self-powered PDs.

Phenethyl Isothiocyanate Induces Apoptotic Cell Death Through the Mitochondria-dependent Pathway in Gefitinib-resistant NCI-H460 Human Lung Cancer Cells In Vitro.

BACKGROUND/AIM: Some lung cancer patients treated with gefitinib develop resistance to this drug resulting in unsatisfactory treatment outcomes. Phenethyl isothiocyanate (PEITC), present in our common cruciferous vegetables, exhibits anticancer activities in many human cancer cell lines. Currently, there is no available information on the possible modification of gefitinib resistance of lung cancer in vitro by PEITC. Thus, the effects of PEITC on gefitinib resistant lung cancer NCI-H460 cells were investigated in vitro. MATERIALS AND METHODS: The total cell viability, apoptotic cell death, production of reactive oxygen species (ROS) and Ca2+, levels of mitochondria membrane potential (ΔΨm) and caspase-3, -8 and -9 activities were measured by flow cytometry assay. PEITC induced chromatin condensation was examined by DAPI staining. RESULTS: PEITC-induced cell morphological changes, decreased total viable cell number and induced apoptotic cell death in NCI-H460 and NCI-H460/G cells. PEITC decreased ROS production in NCI-H460 cells, but increased production in NCI-H460/G cells. PEITC increased Ca2+ production, decreased the levels of ΔΨm and increased caspase-3, -8 and -9 activities in both NCI-H460 and NCI-H460/G cells. Western blotting was used to examine the effect of apoptotic cell death associated protein expression in NCI-H460 NCI-H460/G cells after exposure to PEITC. Results showed that PEITC increased expression of cleaved caspase-3, PARP, GADD153, Endo G and pro-apoptotic protein Bax in NCI-H460/G cells. CONCLUSION: Based on these results, we suggest that PEITC induces apoptotic cell death via the caspase- and mitochondria-dependent pathway in NCI-H460/G cells.

Anticancer effects of cantharidin in A431 human skin cancer (Epidermoid carcinoma) cells in vitro and in vivo.

Cantharidin (CTD), a potential anticancer agent of Traditional Chinese Medicine has cytotxic effects in different human cancer cell lines. The cytotoxic effects of CTD on A431 human skin cancer (epidermoid carcinoma) cells in vitro and in A431 cell xenograft mouse model were examined. In vitro, A431 human skin cell were treated with CTD for 24 and 48 h. Cell phase distribution, ROS production, Ca2+ release, Caspase activity and the level of apoptosis associated proteins were measured. In vivo, A431 cell xenograft mouse model were examined. CTD-induced cell morphological changes and decreased percentage of viable A431 cells via G0/G1 phase arrest and induced apoptosis. CTD-induced G0/G1 phase arrest through the reduction of protein levels of cyclin E, CDK6, and cyclin D in A431 cells. CTD-induced cell apoptosis of A431 cells also was confirm by DNA gel electrophoresis showed CTD-induced DNA fragmentation. CTD reduced the mitochondrial membrane potential and stimulated release of cytochrome c, AIF and Endo G in A431 cells. Flow cytometry demonstrated that CTD increased activity of caspase-8, -9 and -3. However, when cells were pretreated with specific caspase inhibitors activity was reduced and cell viability increased. CTD increased protein levels of death receptors such as DR4, DR5, TRAIL and levels of the active form of caspase-8, -9 and -3 in A431 cells. AIF and Endo G proteins levels were also enhanced by CTD. In vivo studies showed that CTD significantly inhibited A431 cell xenograft tumors in mice. Taken together, these in vitro and in vivo results provide insight into the mechanisms of CTD on cell growth and tumor production. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 723-738, 2017.

Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells.

Glioblastoma is the most common and aggressive primary brain malignancy. Phenethyl isothiocyanate (PEITC), a member of the isothiocyanate family, can induce apoptosis in many human cancer cells. Our previous study disclosed that PEITC induces apoptosis through the extrinsic pathway, dysfunction of mitochondria, reactive oxygen species (ROS)-induced endoplasmic reticulum (ER) stress, and intrinsic (mitochondrial) pathway in human brain glioblastoma multiforme (GBM) 8401 cells. To the best of our knowledge, we first investigated the effects of PEITC on the genetic levels of GBM 8401 cells in vitro. PEITC may induce G0/G1 cell-cycle arrest through affecting the proteins such as cdk2, cyclin E, and p21 in GBM 8401 cells. Many genes associated with cell-cycle regulation of GBM 8401 cells were changed after PEITC treatment: 48 genes were upregulated and 118 were downregulated. The cell-division cycle protein 20 (CDC20), Budding uninhibited by benzimidazole 1 homolog beta (BUB1B), and cyclin B1 were downregulated, and clusterin was upregulated in GBM 8401 cells treated with PEITC. These changes of gene expression can provide the effects of PEITC on the genetic levels and potential biomarkers for glioblastoma. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 176-187, 2017.

Norcantharidin-induced Apoptosis of AGS Human Gastric Cancer Cells Through Reactive Oxygen Species Production, and Caspase- and Mitochondria-dependent Signaling Pathways.

Norcantharidin (NCTD) was purified from mylabris, the dried body of the Chinese blister beetle. NCTD has been shown to exhibit anticancer activities in many human cancer cell lines, but there are no reports to show whether it induces apoptosis of human gastric cancer cells. Therefore, in the present study, we investigated NCTD-induced cell death and associated protein expression in human gastric cancer AGS cells in vitro. Cell morphological changes, viability and cell-cycle distribution were examined and analyzed by phase-contrast microscopy and flow cytometric assays. Flow cytometry was also used to measure the levels of reactive oxygen species (ROS), Ca2+, mitochondrial membrane potential (Ψm) and activity of caspases. The results indicated that NCTD induced cell morphological changes, reduced total viable cell number and induced G0/G1 phase arrest. NCTD also increased ROS production and reduced the Ψm and increased caspase-9 activity in AGS cells. Western blotting also found that NCTD increased the pro-apoptotic proteins such as BCL2-associated X protein (BAX) and BH3 interacting-domain death agonist (BID) and increased the release of cytochrome c, apoptosis inducing factor (AIF) and endonuclease G (Endo G) release from mitochondria in AGS cells. NCTD also significantly increased the expression of active forms of caspase-3 and -8 and -9 and reduced the expression of caspase-4 and -12 in AGS cells. Based on these observations, we suggest that NCTD-induced apoptotic cell death may be through mitochondria- and caspase-dependent pathways.