Sodium butyrate (NaBu) is a short-chain fatty acid which serves as a histon deacetylase inhibitor and has received considerable interest as a possible regulator of cancer cell death. The regulatory ...effect of NaBu on cancer cell growth or death has yet to be illustrated in many cancers including breast cancer. This study is aimed to elucidate the possible effect of NaBu on regulation of breast cancer growth and apoptosis.
The cytotoxic effect of NaBu on the growth of breast cancer cells (MCF-7 and MDA-MB-468) and normal breast cells (MCF-10A) was determined using MTT assay. Annexin-V-FITC staining and PI staining were performed to detect apoptosis and cell cycle distribution using Flow cytometry, the level of mitochondrial membrane potential (Δψm), Reactive oxygen species (ROS)formation and caspase activity were determined accordingly.
Based on our data, NaBu induced a dose and time-dependent cell toxicity in breast cancer cells which was related to the cell cycle arrest and induction of apoptosis. The impact of NaBu on MCF-10A cell toxicity, cell cycle distribution and apoptosis was inconsiderable. NaBu-elicited apoptosis was accompanied by the elevated level of ROS, increased caspase activity and reduced mitochondrial membrane potential (Δψm) in MCF-7 and MDA-MB-468 cells and with no effect on the above mentioned factors in MCF-10A cells.
Our study provided insight in to the role of NaBu on the regulation of breast cancer cell growth and lighten up the pro-apoptotic activity of NaBu.
The expression pattern of the opioid receptor (MOR) in pituitary neuroendocrine tumors (PitNET) and the possible effect of morphine and naloxone on GH3 cell growth and apoptosis were evaluated.
The ...114 pituitary tissues including non-functioning, GH-producing and ACTH-producing PitNET and healthy cadaver pituitary tissues were included. The expression level of the MOR gene and protein was assessed using real-time PCR and Western blot. The association with patient demographic characteristics was assessed. Morphine and naloxone were applied to assess their possible pharmacological role in GH3 pituitary adenoma cell death. The cytotoxic effect, the apoptosis rate, the cell cycle distribution, the content of reactive oxygen species and the caspase 3 activity were measured.
MOR gene levels increased significantly in pituitary neuroendocrine tumors (PitNET) compared to the healthy pituitary samples. The increased level of MOR gene expression was prominent in invasive functional and non-functional pituitary tumors. A consistent expression pattern was demonstrated for MOR protein levels in PitNET samples. A dose- and time-dependent reduction in the rate of GH3 pituitary cells was observed after morphine treatment with an IC50 of 483 µM after 24 h of incubation. Morphine induced early apoptosis, accumulation of cells in sub-G1 phase, increase in cellular ROS levels and caspase-3 activity. The observed effects of morphine were reversed after MOR blockade using 10 and 25 µM naloxone.
The possible contributing role of the MOR in pituitary tumor cell growth and the putative pharmaceutical effect of morphine in pituitary neuroendocrine tumor cell death (PitNET) is illustrated
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Glioblastoma multiforme (GBM) is one of the deadliest cancers. Temozolomide (TMZ) is the most common chemotherapy used for GBM patients. Recently, combination chemotherapy strategies have had more ...effective antitumor effects and focus on slowing down the development of chemotherapy resistance. A combination of TMZ and cholesterol-lowering medications (statins) is currently under investigation in in vivo and clinical trials. In our current investigation, we have used a triple-combination therapy of TMZ, Simvastatin (Simva), and acetylshikonin, and investigated its apoptotic mechanism in GBM cell lines (U87 and U251). We used viability, apoptosis, reactive oxygen species, mitochondrial membrane potential (MMP), caspase-3/-7, acridine orange (AO) and immunoblotting autophagy assays. Our results showed that a TMZ/Simva/ASH combination therapy induced significantly more apoptosis compared to TMZ, Simva, ASH, and TMZ/Simva treatments in GBM cells. Apoptosis via TMZ/Simva/ASH treatment induced mitochondrial damage (increase of ROS, decrease of MMP) and caspase-3/7 activation in both GBM cell lines. Compared to all single treatments and the TMZ/Simva treatment, TMZ/Simva/ASH significantly increased positive acidic vacuole organelles. We further confirmed that the increase of AVOs during the TMZ/Simva/ASH treatment was due to the partial inhibition of autophagy flux (accumulation of LC3β-II and a decrease in p62 degradation) in GBM cells. Our investigation also showed that TMZ/Simva/ASH-induced cell death was depended on autophagy flux, as further inhibition of autophagy flux increased TMZ/Simva/ASH-induced cell death in GBM cells. Finally, our results showed that TMZ/Simva/ASH treatment potentially depends on an increase of Bax expression in GBM cells. Our current investigation might open new avenues for a more effective treatment of GBM, but further investigations are required for a better identification of the mechanisms.
A supramolecular dimeric complex Ag(dppf)(NO
3
)
2
was prepared via the reaction of a solution of AgNO
3
in methanol/dichloromethane with 1,1′-bis(diphenylphosphino)ferrocene (dppf) which was fully ...characterized by IR, elemental analysis, multinuclear NMR (
1
H,
13
C and
31
P) spectroscopy and X-ray crystal structure determination. The crystal structure of new complex Ag(μ-dppf)(NO
3
)
2
⋅4CHCl
3
reveals that the coordination geometry about each Ag(I) center in the dimeric complex is 4 + 1 polyhedron. As well, the crystal packing of complex Ag(μ-dppf)(NO
3
)
2
⋅4CHCl
3
clearly shows the formation of a supramolecular network through C–H⋯X (X = N, O, Cl) hydrogen bond interactions in which the asymmetric unit contains two independent molecules of Ag(μ-dppf)(NO
3
)
2
⋅4CHCl
3
. Both independent molecules related by inversion to form the dimeric silver complex with Ag⋯Ag distances of 4.000 and 4.0235 Å. Hirshfeld surface analysis of the structure as well as its fingerprints were used to identify and quantify the inter–molecular interactions of hydrogen bonds. Luminescence properties of the supramolecular silver complex were assigned to π–π* transitions in different solvents. Thermal properties of this complex showed a three-step decomposition. The cytotoxic properties of this complex were also studied using MTT assays against MCF-7 human breast cancer, U87-MG human glioblastoma, HT-29 human colorectal cancer, and SCOV-3 human ovarian cancer cell lines in comparison with AGO1522 human normal skin fibroblast cell line. The supramolecular silver complex exhibited higher cytotoxic effects (lower IC
50
) against U87-MG, MCF-7, HT-29 and SCOV-3 cancer cell lines in comparison with AGO1522.
Pituitary adenomas impose a burden of morbidity on patients and characterizing the molecular mechanisms underlying its pathogenesis received remarkable attention. Despite the appealing role of ...necroptosis as an alternative cell death pathway in cancer pathogenesis, its relevance to pituitary adenoma pathogenesis has yet to be determined that is perused in the current study.
The total number of 109 specimens including pituitary adenomas and cadaveric healthy pituitary tissues were enrolled in the current study. Tumor and healthy pituitary tissues were subjected to RNA extraction and gene analysis using Real-Time PCR. The expression levels of necroptosis markers (RIP1K, RIP3K and, MLKL) and their association with the patient's demographic features were evaluated, also the protein level of MLKL was assessed using immunohistochemistry in tissues.
Based on our data, the remarkable reduction in RIP3K and MLKL expression were detected in nonfunctional and GH-secreting pituitary tumors compared to pituitary normal tissues. Invasive tumors revealed lower expression of RIP3K and MLKL compared to non-invasive tumors, also the attenuated level of MLKL was associated with the tumor size in invasive NFPA. The simultaneous down-regulation of MLKL protein in pituitary adenoma tissues was observed which was in line with its gene expression. While, RIP1K over-expressed significantly in both types of pituitary tumors which showed no significant correlation with patient's age, gender and tumor size in GHPPA and NFPA group. Notably, MLKL and RIP3K gene expression was significantly correlated in the GHPPA group.
According to our data, the reduced expression of necroptosis mediators (RIP3K, MLKL) in pituitary adenoma reinforces the hypothesis that the necroptosis pathway can be effective in regulating the proliferation and growth of pituitary tumor cells and tumor recurrence.
Over the past few decades, biological hazards and organic pollution have become major environmental concerns. Photocatalysis has been found to be effective in minimizing the negative impacts of these ...issues in air and water. Lozenge shape Ag/AgCl/ZnTiO3 photocatalysts were fabricated by a facile two-step synthesis method, including hydrothermal and coprecipitation. The physicochemical characteristics and morphological properties of the structures were comprehensively described taking advantage of a multi-technique approach. The prepared photocatalysts offered excellent nitrophenol mineralization (>90%) after 90 min of visible light irradiation. Based on the spin-trapping ESR technique, •O2̅– was recognized as the eminent reactive species during the photocatalytic process. Interestingly, the plasmonic Ag/AgCl/ZnTiO3 photocatalyst presented promising CO2 to CO/CH4 conversion with a production rate of 95.0/18.5 μmol.g−1.h−1 under visible light irradiation, which is about 1.6 times higher than that of ZnTiO3, implying the synergetic effects due to Ag/AgCl in the ternary construction. In addition to the investigation of antibacterial activity, the prepared photocatalysts were successfully applied to treat the hazardous biological waste bearing U87-MG cancer cells under visible light for the first time. Several as-related analytical techniques were served to demonstrate the activity and interaction pathways. This work may hone a new insight into designing highly efficacious ternary photocatalytic materials.
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•Fabrication of novel lozenge shape Ag/AgCl@ZnTiO3 photocatalysts.•Efficient photocatalytic removal of nitrophenols under visible light.•Productive conversion of CO2 to CO/CH4 over the photocatalysts.•Efficient treatment of the biological waste by the photocatalysts.•Mechanistic discussion of the photocatalytic pathways based on promising techniques.
Background. Medicinal plants have been remarkable sources of current chemotherapeutic agents. Ethnobotanical utilization of Bryonia species goes back to the old era, and contemporary but preliminary ...studies have evidenced the anticancer effects of this kind of plant. Methods. The MTT assay was used to investigate the cytotoxicity of a range of concentrations from different extracts of Bryonia aspera root in cancer and noncancer cells. The apoptosis was assessed using annexinV-FITC/PI flow cytometry assay. The expression of selected hallmark genes from different cell death modalities, including apoptosis, necroptosis, ferroptosis, and pyroptosis, was investigated using the qPCR method. The ROS production was also measured by the fluorescence technique. Results. Compared to the normal cells, all three extracts could induce significant cell death in lower doses in breast, ovarian, and glioblastoma cancer cells. Flow cytometry and gene expression studies revealed that different extracts of Bryonia aspera tend to induce different types of cell death in the selective cancer cell lines. ROS production was not impacted significantly by any of those three extracts in none of the cancer cells. Conclusion. The findings showed that all three extracts of Bryonia aspera root contain biologically active compounds that induce different types of programmed cell death in the investigated breast, ovarian, and glioblastoma cancer cells in concentrations significantly less than the doses affecting normal cells.
Resistance to cell death and reprogramming of metabolism are important in neoplastic cells. Increased resistance to apoptosis and recurrence of tumors are the major roadblocks to effective treatment ...of triple negative breast cancer. It has been thought that execution of necroptosis involves ROS generation and mitochondrial dysfunction in malignant cells. In this study, the effect of shikonin, an active substance from the dried root of
Lithospermum erythrorhizon
, on the induction of necroptosis or apoptosis, via RIP1K-RIP3K expressions has been examined in the triple negative breast cancer cell line. The expression levels of RIP1K and RIP3K, caspase-3 and caspase-8 activities, the levels of ROS, and mitochondrial membrane potential have been studied in the shikonin-treated MDA-MB-468 cell line. An increase in the ROS levels and a reduction in mitochondrial membrane potential have been observed in the shikonin-treated cells. Cell death has mainly occurred through necroptosis with a significant increase in the RIP1K and RIP3K expressions, and characteristic morphological changes have been observed. In the presence of Nec-1, caspase-3 mediating apoptosis has occurred in the shikonin-treated cells. The current findings have revealed that shikonin provoked mitochondrial ROS production in the triple negative breast cancer cell line, which works as a double-edged executioner’s ax in the execution of necroptosis or apoptosis. The main route of cell death induced by shikonin is RIP1K-RIP3K-mediated necroptosis, but in the presence of Nec-1, apoptosis has prevailed. The present results shed a new light on the possible treatment of drug-resistant triple negative breast cancer.
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