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Ethiopian Journal of Health Sciences Jul 2023Arsenic trioxide is an activist agent in the treatment of acute promyelocytic leukemia (APL), which acts alone, but has an adverse effect on patients. Moreover,...
BACKGROUND
Arsenic trioxide is an activist agent in the treatment of acute promyelocytic leukemia (APL), which acts alone, but has an adverse effect on patients. Moreover, deferoxamine has antiproliferative activity and induces leukopenia. In order to enhance antileukemic effectiveness and to reduce the dosage of arsenic trioxide, the combination effect of it with deferoxamine (DFO) was evaluated on the APL cell line (NB4).
METHODS
In this experimental study, to investigate the cytotoxic effects of ATO/DFO in acute promyelocytic leukemia, the NB4 cell line (provided by Pasteur Institute of Iran) was treated with different doses and then at 24, 48, and 72 hrs intervals, the percentage of survival, cell count, metabolic activity and apoptosis induction were investigated respectively. Also, hTERT gene expression was analyzed by the RT-PCR method.
RESULTS
We found that DFO alone and in combination with ATO has cytotoxic and antiproliferative effects, and reduces viability and cell metabolic activity in the NB4 cell line in a dose and time-dependent manner. In addition, this combination causes an increase in apoptosis, up-regulation of Caspase-3, and down-regulation of hTERT genes in cells.
CONCLUSION
Combined ATO/ DFO treatment cooperatively decreased the mRNA levels of the hTERT and increased the mRNA levels of Caspase-3 in a time-dependent manner compared to DFO alone.
Topics: Arsenic Trioxide; Humans; Arsenicals; Leukemia, Promyelocytic, Acute; Deferoxamine; Cell Survival; Cell Line, Tumor; Apoptosis; Telomerase; Oxides; Antineoplastic Agents; Cell Proliferation
PubMed: 38784214
DOI: 10.4314/ejhs.v33i4.17 -
PeerJ 2024Promoter hypermethylation of the tumor suppressor gene is one of the well-studied causes of cancer development. The drugs that reverse the process by driving...
BACKGROUND
Promoter hypermethylation of the tumor suppressor gene is one of the well-studied causes of cancer development. The drugs that reverse the process by driving demethylation could be a candidate for anticancer therapy. This study was designed to investigate the effects of arsenic disulfide on methylation in diffuse large B cell lymphoma (DLBCL).
METHODS
We knocked down the expression of in two DLBCL cell lines (, DB and SU-DHL-4 cells) using siRNA. Then the DLBCL proliferation was determined in the presence of knockdown. The methylation of in DLBCL cells was analyzed by methylation specific PCR (MSPCR). The effect of arsenic disulfide on the methylation was determined in DLBCL cell lines in the presence of different concentrations of arsenic disulfide (5 µM, 10 µM and 20 µM), respectively. To investigate the potential mechanism on the arsenic disulfide-mediated methylation, the mRNA expression of , and was determined.
RESULTS
functioned as a tumor suppressor gene in DLBCL cells, which was featured by the fact that knockdown promoted the proliferation of DLBCL cells. was found hypermethylated in DLBCL cells. Arsenic disulfide promoted the demethylation in a dose-dependent manner, which was related to the inhibition of DNMTs and the increase of MBD2.
CONCLUSION
Experimental evidence shows that functions as a tumor suppressor gene in DLBCL progression. hyper-methylation could be reversed by arsenic disulfide in a dose-dependent manner.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Cell Line, Tumor; DNA Methylation; Cell Proliferation; Arsenicals; DNA Methyltransferase 3B; Disulfides; DNA (Cytosine-5-)-Methyltransferases; DNA (Cytosine-5-)-Methyltransferase 1; DNA-Binding Proteins; Gene Knockdown Techniques; Promoter Regions, Genetic; Gene Expression Regulation, Neoplastic
PubMed: 38766487
DOI: 10.7717/peerj.17363 -
Journal of Ethnopharmacology Sep 2024Realgar, a traditional mineral Chinese medicine, has been used in China for more than 2000 years. It has been recorded in many ancient and modern works that it has...
ETHNOPHARMACOLOGICAL RELEVANCE
Realgar, a traditional mineral Chinese medicine, has been used in China for more than 2000 years. It has been recorded in many ancient and modern works that it has anti-cancer and anti-tumor effects. Of course, colon cancer is also within the scope of its treatment. Realgar needs to be processed into realgar decoction pieces by water grinding before being used for medicine. To ensure the consistency of efficacy and quality of realgar decoction pieces, modern methods need to be used for further quality control.
AIM OF THE STUDY
The research of traditional mineral Chinese medicine is relatively difficult, and the related research is less. The purpose of this study is to control the quality of realgar decoction pieces by modern analytical technology and analyze its components. On this basis, its anti-colon cancer activity was discussed.
MATERIALS AND METHODS
Several batches of realgar decoction pieces were analyzed by XRD, and the components of realgar decoction pieces were obtained. The quality control fingerprints of realgar decoction pieces were established by processing XRD spectra and similarity evaluation. Then, the effects of realgar decoction pieces on apoptosis of CT26 and HTC-116 cells were observed in vitro by Hoechst 33258 staining, flow cytometry, measurement of mitochondrial membrane potential and Western blot; In vivo, the mouse model of tumor-in-situ transplantation of colon cancer was established, and the related indexes were observed.
RESULT
The explorations showed that the XRD Fourier fingerprints of realgar decoction pieces samples that had the same phase revealed 10 common peaks, respectively. The similarity evaluation of the established XRD Fourier fingerprint was greater than 0.900. We also demonstrated that realgar decoction pieces can promote apoptosis and inhibit tumor growth in colon cancer cells, its activating effect on p53 protein, and its safety when used within reasonable limits.
CONCLUSION
The quality control of realgar decoction pieces by XRD is scientific and has the inhibitory effect on colon cancer, which has the development potential.
Topics: Animals; Apoptosis; Mice; Colonic Neoplasms; Humans; Sulfides; Arsenicals; Antineoplastic Agents; Drugs, Chinese Herbal; Cell Line, Tumor; Mice, Inbred BALB C; Membrane Potential, Mitochondrial; Male; Quality Control; Antineoplastic Agents, Phytogenic
PubMed: 38734390
DOI: 10.1016/j.jep.2024.118303 -
PloS One 2024Although the toxicity of arsenic depends on its chemical forms, few studies have taken into account the ambiguous phenomenon that sodium arsenite (NaAsO2) acts as a...
Sodium arsenite and arsenic trioxide differently affect the oxidative stress of lymphoblastoid cells: An intricate crosstalk between mitochondria, autophagy and cell death.
Although the toxicity of arsenic depends on its chemical forms, few studies have taken into account the ambiguous phenomenon that sodium arsenite (NaAsO2) acts as a potent carcinogen while arsenic trioxide (ATO, As2O3) serves as an effective therapeutic agent in lymphoma, suggesting that NaAsO2 and As2O3 may act via paradoxical ways to either promote or inhibit cancer pathogenesis. Here, we compared the cellular response of the two arsenical compounds, NaAsO2 and As2O3, on the Burkitt lymphoma cell model, the Epstein Barr Virus (EBV)-positive P3HR1 cells. Using flow cytometry and biochemistry analyses, we showed that a NaAsO2 treatment induces P3HR1 cell death, combined with drastic drops in ΔΨm, NAD(P)H and ATP levels. In contrast, As2O3-treated cells resist to cell death, with a moderate reduction of ΔΨm, NAD(P)H and ATP. While both compounds block cells in G2/M and affect their protein carbonylation and lipid peroxidation, As2O3 induces a milder increase in superoxide anions and H2O2 than NaAsO2, associated to a milder inhibition of antioxidant defenses. By electron microscopy, RT-qPCR and image cytometry analyses, we showed that As2O3-treated cells display an overall autophagic response, combined with mitophagy and an unfolded protein response, characteristics that were not observed following a NaAsO2 treatment. As previous works showed that As2O3 reactivates EBV in P3HR1 cells, we treated the EBV- Ramos-1 cells and showed that autophagy was not induced in these EBV- cells upon As2O3 treatment suggesting that the boost of autophagy observed in As2O3-treated P3HR1 cells could be due to the presence of EBV in these cells. Overall, our results suggest that As2O3 is an autophagic inducer which action is enhanced when EBV is present in the cells, in contrast to NaAsO2, which induces cell death. That's why As2O3 is combined with other chemicals, as all-trans retinoic acid, to better target cancer cells in therapeutic treatments.
Topics: Arsenic Trioxide; Arsenites; Humans; Oxidative Stress; Mitochondria; Sodium Compounds; Arsenicals; Autophagy; Cell Line, Tumor; Oxides; Cell Death; Membrane Potential, Mitochondrial; Herpesvirus 4, Human; Adenosine Triphosphate; Hydrogen Peroxide; Lipid Peroxidation; Burkitt Lymphoma
PubMed: 38728286
DOI: 10.1371/journal.pone.0302701 -
Carbohydrate Polymers Aug 2024In vivo, cells interact with the extracellular matrix (ECM), which provides a multitude of biophysical and biochemical signals that modulate cellular behavior. Inspired...
In vivo, cells interact with the extracellular matrix (ECM), which provides a multitude of biophysical and biochemical signals that modulate cellular behavior. Inspired by this, we explored a new methodology to develop a more physiomimetic polysaccharide-based matrix for 3D cell culture. Maleimide-modified alginate (AlgM) derivatives were successfully synthesized using DMTMM to activate carboxylic groups. Thiol-terminated cell-adhesion peptides were tethered to the hydrogel network to promote integrin binding. Rapid and efficient in situ hydrogel formation was promoted by thiol-Michael addition "click" chemistry via maleimide reaction with thiol-flanked protease-sensitive peptides. Alginate derivatives were further ionically crosslinked by divalent ions present in the medium, which led to greater stability and allowed longer cell culture periods. By tailoring alginate's biofunctionality we improved cell-cell and cell-matrix interactions, providing an ECM-like 3D microenvironment. We were able to systematically and independently vary biochemical and biophysical parameters to elicit specific cell responses, creating custom-made 3D matrices. DMTMM-mediated maleimide incorporation is a promising approach to synthesizing AlgM derivatives that can be leveraged to produce ECM-like matrices for a broad range of applications, from in vitro tissue modeling to tissue regeneration.
Topics: Click Chemistry; Maleimides; Alginates; Sulfhydryl Compounds; Hydrogels; Extracellular Matrix; Humans; Cross-Linking Reagents; Cell Adhesion; Animals
PubMed: 38710569
DOI: 10.1016/j.carbpol.2024.122144 -
Frontiers in Public Health 2024An increasing number of studies suggest that environmental pollution may increase the risk of vitamin D deficiency (VDD). However, less is known about arsenic (As)...
BACKGROUND
An increasing number of studies suggest that environmental pollution may increase the risk of vitamin D deficiency (VDD). However, less is known about arsenic (As) exposure and VDD, particularly in Chinese pregnant women.
OBJECTIVES
This study examines the correlations of different urinary As species with serum 25 (OH) D and VDD prevalence.
METHODS
We measured urinary arsenite (As), arsenate (As), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) levels and serum 25(OH)D, 25(OH)D, 25(OH) D levels in 391 pregnant women in Tianjin, China. The diagnosis of VDD was based on 25(OH) D serum levels. Linear relationship, Logistic regression, and Bayesian kernel machine regression (BKMR) were used to examine the associations between urinary As species and VDD.
RESULTS
Of the 391 pregnant women, 60 received a diagnosis of VDD. Baseline information showed significant differences in As, DMA, and tAs distribution between pregnant women with and without VDD. Logistic regression showed that As was significantly and positively correlated with VDD (OR: 4.65, 95% CI: 1.79, 13.32). Meanwhile, there was a marginally significant positive correlation between tAs and VDD (OR: 4.27, 95% CI: 1.01, 19.59). BKMR revealed positive correlations between As, MMA and VDD. However, negative correlations were found between As, DMA and VDD.
CONCLUSION
According to our study, there were positive correlations between iAs, especially As, MMA and VDD, but negative correlations between other As species and VDD. Further studies are needed to determine the mechanisms that exist between different As species and VDD.
Topics: Humans; Female; Vitamin D Deficiency; Pregnancy; Cross-Sectional Studies; China; Adult; Arsenic; Prevalence; Arsenicals; Vitamin D; Pregnancy Complications; Logistic Models; East Asian People
PubMed: 38694994
DOI: 10.3389/fpubh.2024.1371920 -
Scientific Reports Apr 2024Phthorimaea absoluta is an invasive solanaceous plant pest with highly devastating effects on tomato plant. Heavy reliance on insecticide use to tackle the pest has been...
Phthorimaea absoluta is an invasive solanaceous plant pest with highly devastating effects on tomato plant. Heavy reliance on insecticide use to tackle the pest has been linked to insecticide resistance selection in P. absoluta populations. To underline insights on P. absoluta insecticide resistance mechanisms to diamides and avermectins, we evaluated the transcriptomic profile of parental (field-collected) and F8 (lab-reared) populations. Furthermore, to screen for the presence of organophosphate and pyrethroid resistance, we assessed the gene expression levels of acetylcholinesterase (ace1) and para-type voltage-gated sodium channel (VGSG) genes in the F1 to F8 lab-reared progeny of diamide and avermectin exposed P. absoluta field-collected populations. The VGSG gene showed up-regulation in 12.5% and down-regulation in 87.5% of the screened populations, while ace1 gene showed up-regulation in 37.5% and down-regulation in 62.5% of the screened populations. Gene ontology of the differentially expressed genes from both parental and eighth generations of diamide-sprayed P. absoluta populations revealed three genes involved in the metabolic detoxification of diamides in P. absoluta. Therefore, our study showed that the detoxification enzymes found could be responsible for P. absoluta diamide-based resistance, while behavioural resistance, which is stimulus-dependent, could be attributed to P. absoluta avermectin resistance.
Topics: Animals; Lepidoptera; Insecticides; Moths; Acetylcholinesterase; Diamide; Gene Expression Profiling; Larva; Ivermectin
PubMed: 38575641
DOI: 10.1038/s41598-024-58413-z -
Biochemistry Apr 2024Ferroptosis is a recently identified form of regulated cell death, characterized by excessive iron-dependent lipid peroxidation. Recent studies have demonstrated that...
Strong Protection by 4-Hydroxyestrone against Erastin-Induced Ferroptotic Cell Death in Estrogen Receptor-Negative Human Breast Cancer Cells: Evidence for Protein Disulfide Isomerase as a Mechanistic Target for Protection.
Ferroptosis is a recently identified form of regulated cell death, characterized by excessive iron-dependent lipid peroxidation. Recent studies have demonstrated that protein disulfide isomerase (PDI) is an important mediator of chemically induced ferroptosis and also a new target for protection against ferroptosis-associated cell death. In the present study, we identified that 4-hydroxyestrone (4-OH-E), a metabolic derivative of endogenous estrogen, is a potent small-molecule inhibitor of PDI, and can strongly protect against chemically induced ferroptotic cell death in the estrogen receptor-negative MDA-MB-231 human breast cancer cells. Pull-down and CETSA assays demonstrated that 4-OH-E can directly bind to PDI both in vitro and in intact cells. Computational modeling analysis revealed that 4-OH-E forms two hydrogen bonds with PDI His256, which is essential for its binding interaction and thus inhibition of PDI's catalytic activity. Additionally, PDI knockdown attenuates the protective effect of 4-OH-E as well as cystamine (a known PDI inhibitor) against chemically induced ferroptosis in human breast cancer cells. Importantly, inhibition of PDI by 4-OH-E and cystamine or PDI knockdown by siRNAs each markedly reduces iNOS activity and NO accumulation, which has recently been demonstrated to play an important role in erastin-induced ferroptosis. In conclusion, this study demonstrates that 4-OH-E is a novel inhibitor of PDI and can strongly inhibit ferroptosis in human breast cancer cells in an estrogen receptor-independent manner. The mechanistic understanding gained from the present study may also aid in understanding the estrogen receptor-independent cytoprotective actions of endogenous estrogen metabolites in many noncancer cell types.
Topics: Humans; Female; Protein Disulfide-Isomerases; Breast Neoplasms; Cystamine; Cell Death; Estrogens; Receptors, Estrogen; Hydroxyestrones; Piperazines
PubMed: 38569593
DOI: 10.1021/acs.biochem.3c00261 -
Molecules (Basel, Switzerland) Mar 2024The meta-diamide (-diamide) insecticide, Broflanilide, was characterized by its high efficiency, low toxicity and lack of cross-resistance with traditional GABA...
The meta-diamide (-diamide) insecticide, Broflanilide, was characterized by its high efficiency, low toxicity and lack of cross-resistance with traditional GABA receptors. In accordance with the principles of drug molecular design, easily derivable sulfur with diverse bioactivities was introduced while leading with the parent Broflanilide. Twelve novel -diamide target compounds containing sulfide derivatives were synthesized through exploration guided by the literature. Their structures were confirmed by melting points, H NMR, C NMR and HRMS. Insecticidal activity assessments revealed that most target compounds - exhibited 100% lethality against () and () at 500 mg·L. Notably, for , compounds , , and demonstrated 60.00-100.00% insecticidal activity even at a concentration as low as 0.625 mg·L. As determined by structure-activity relationship (SAR) analysis, compounds with R = CH and R = Br (, and ) and sulfoxide compound contained 100.00% lethality against at 500 mg·L, surpassing the lethality when leading with the parent Broflanilide in terms of efficacy. Consequently, it can be inferred that the sulfoxide compound () requires further investigation as a potential active molecule for new insecticides. These explorations provide valuable references for future research on the synthesis and insecticidal activities of sulfide-containing -diamide compounds.
Topics: Animals; Molecular Structure; Pesticides; Diamide; Moths; Structure-Activity Relationship; Insecticides; Sulfoxides; Benzamides; Fluorocarbons
PubMed: 38542973
DOI: 10.3390/molecules29061337 -
International Journal of Molecular... Mar 2024Previous studies have shown that inorganic arsenic (iAs) exposure may be associated with genotoxic and cytotoxic effects. The aim of this study was to evaluate the...
Previous studies have shown that inorganic arsenic (iAs) exposure may be associated with genotoxic and cytotoxic effects. The aim of this study was to evaluate the relationship between several polymorphisms in and genes and urinary As and the relationship between these polymorphisms and pregnancy loss. We determined urinary As concentrations and performed genotyping analysis in 50 cases of spontaneous pregnancy loss and 50 controls, matched to cases on gestational age. The most frequently identified polymorphisms in both cases and controls were in rs10748835 (80% cases and 68% controls), rs3740400 (78% cases and 64% controls), rs7085104 (74% cases and 48% controls), and rs1046778 (62% cases and 54% controls). We identified 30 different haplotypes in SNPs, with four predominant haplotypes (>8%). Cases with Haplotype 1 had four-fold higher urinary DMA and two-fold higher MMA concentration than those without this haplotype, the MMA levels were lower in cases and controls with Haplotype 4 compared to Haplotype 1, and the DMA levels were significantly lower in cases with Haplotype 4 compared to Haplotype 3. Cases with Haplotype 1 had higher levels of all analyzed biomarkers, suggesting that Haplotype 1 may be associated with greater exposure to iAs and tobacco smoke. Our results suggest the importance of the gene in iAs metabolism among pregnant women with low-level drinking water iAs exposure.
Topics: Humans; Female; Pregnancy; Arsenic; Methyltransferases; Drinking Water; Pregnant Women; Romania; Abortion, Spontaneous; Arsenicals; Polymorphism, Single Nucleotide; Apolipoproteins E
PubMed: 38542322
DOI: 10.3390/ijms25063349