Displaying publications 41 - 60 of 190 in total

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  1. Fulltext Experimental exposure of Burkholderia pseudomallei crude culture filtrate upregulates PD-1 on T lymphocytes
    Menon N, Mariappan V, Vellasamy KM, Samudi C, See JX, Ganesh PS, et al.
    Access Microbiol, 2020;2(5):acmi000110.
    PMID: 32974575 DOI: 10.1099/acmi.0.000110
    Burkholderia pseudomallei is the causative agent for melioidosis. Because of its intracellular nature, the bacterium is capable of replicating within a plethora of eukaryotic cell lines. B. pseudomallei can remain dormant within host cells without symptoms for years, causing recrudescent infections. Here, we investigated the pathogenesis mechanism behind the suppression of T cell responses by B. pseudomallei . Peripheral blood mononuclear cells (1×106 cells/well) isolated by Ficoll Paque (Sigma-Aldrich) density gradient centrifugation were incubated with optimized concentrations of bacterial crude culture filtrate antigens (CFAs) (10 ug ml-1) and heat-killed bacteria [1 : 10 multiplicity of infection (m.o.i.)]. Following incubation, cells were investigated for surface expression of coinhibitory molecules by flow cytometry. We found that B. pseudomallei induced the upregulation of programmed death 1 (PD-1), a molecule responsible for T cell exhaustion, on T cells in vitro following exposure to crude CFAs of B. pseudomallei . This upregulation of PD-1 probably contributes to poor immune surveillance and disease pathogenesis.
    Matched MeSH terms: Programmed Cell Death 1 Receptor
  2. Pereskia bleo Leaves Extract Induces Cell Death via Cell Cycle Arrest and Apoptosis in Cervical Cancer Cells HeLa
    Mohd-Salleh SF, Wan-Ibrahim WS, Ismail N
    Nutr Cancer, 2020;72(5):826-834.
    PMID: 31433251 DOI: 10.1080/01635581.2019.1654530
    Introduction:Pereskia bleo is a leafy and edible plant, locally known as "Pokok Jarum Tujuh Bilah" which has anticancer properties. This study purposed to determine the cytotoxic effects of P. bleo leaves extracts on several well-known cancer cells and elucidate its underlying mechanism in inducing cell death.Methods: Cytotoxic activity on selected cell lines was determined using MTT assay. Mechanism of cell death was investigated through cell cycle and Annexin V assay. Expression of apoptotic proteins was measured by flow cytometry method.Results: Ethyl acetate extract of P. bleo leaves (PBEA) appeared to have the strongest IC50 value (14.37 ± 8.40 μg/ml) and most active against HeLa cells was further studied for apoptosis. The cell cycle investigation by flow cytometry evidenced the increment of PBEA treated HeLa cells in G0/G1 phase and apoptotic event was detected in Annexin V assay. Analysis of apoptotic protein showed pro-apoptotic proteins (Bax, p53 and caspase 3) were triggered where as anti-apoptotic protein Bcl-2 was suppressed in treated HeLa cells.Conclusions: Our findings demonstrated that PBEA treatment induced cell death in HeLa cells by p53-mediated mechanism through arresting cell cycle at G0/G1 phase and mitochondrial-mediated pathway with involvement of pro-apoptotic proteins, anti-apoptotic protein, and caspase 3.
    Matched MeSH terms: Cell Death/drug effects
  3. Fulltext Antibacterial Activity and Mode of Action of β-caryophyllene on Bacillus cereus
    Moo CL, Yang SK, Osman MA, Yuswan MH, Loh JY, Lim WM, et al.
    Pol J Microbiol, 2020;69:1-6.
    PMID: 32162852 DOI: 10.33073/pjm-2020-007
    Natural products such as essential oils (EOs) are secondary metabolites that can be obtained from either plant or animal sources or produced by microorganisms. Much attention has been given to exploring the use of secondary metabolites as natural antibacterial agents. This study investigates the antibacterial activity and mechanism of β-caryophyllene, a compound that can be found in various EOs, against Bacillus cereus. The minimum inhibitory concentration of β-caryophyllene against B. cereus was 2.5% (v/v), whereas killing kinetics of β-caryophyllene at minimum inhibitory concentration recorded complete bactericidal activity within 2 hours. Zeta-potential measurement in the cells treated with half the minimum inhibitory concentration of β-caryophyllene at 1.25% (v/v) showed an increase in the membrane permeability surface charge to -3.98 mV, compared to untreated cells (-5.46 mV). Intracellular contents leakage of UV-absorbing materials was detected in the cells treated with β-caryophyllene. Additionally, β-caryophyllene does not interfere with the efflux activity of B. cereus via the ethidium bromide influx/efflux activity. The results revealed that β-caryophyllene was able to alter membrane permeability and integrity of B. cereus, leading to membrane damage and intracellular content leakage, which eventually caused cell death.

    Natural products such as essential oils (EOs) are secondary metabolites that can be obtained from either plant or animal sources or produced by microorganisms. Much attention has been given to exploring the use of secondary metabolites as natural antibacterial agents. This study investigates the antibacterial activity and mechanism of β-caryophyllene, a compound that can be found in various EOs, against Bacillus cereus. The minimum inhibitory concentration of β-caryophyllene against B. cereus was 2.5% (v/v), whereas killing kinetics of β-caryophyllene at minimum inhibitory concentration recorded complete bactericidal activity within 2 hours. Zeta-potential measurement in the cells treated with half the minimum inhibitory concentration of β-caryophyllene at 1.25% (v/v) showed an increase in the membrane permeability surface charge to –3.98 mV, compared to untreated cells (–5.46 mV). Intracellular contents leakage of UV-absorbing materials was detected in the cells treated with β-caryophyllene. Additionally, β-caryophyllene does not interfere with the efflux activity of B. cereus via the ethidium bromide influx/efflux activity. The results revealed that β-caryophyllene was able to alter membrane permeability and integrity of B. cereus, leading to membrane damage and intracellular content leakage, which eventually caused cell death.

    Matched MeSH terms: Cell Death
  4. Fulltext Predisposition to Alzheimer's and Age-Related Brain Pathologies by PM2.5 Exposure: Perspective on the Roles of Oxidative Stress and TRPM2 Channel
    Wang L, Wei LY, Ding R, Feng Y, Li D, Li C, et al.
    Front Physiol, 2020;11:155.
    PMID: 32174842 DOI: 10.3389/fphys.2020.00155
    Accumulating epidemiological evidence supports that chronic exposure to ambient fine particular matters of <2.5 μm (PM2.5) predisposes both children and adults to Alzheimer's disease (AD) and age-related brain damage leading to dementia. There is also experimental evidence to show that PM2.5 exposure results in early onset of AD-related pathologies in transgenic AD mice and development of AD-related and age-related brain pathologies in healthy rodents. Studies have also documented that PM2.5 exposure causes AD-linked molecular and cellular alterations, such as mitochondrial dysfunction, synaptic deficits, impaired neurite growth, neuronal cell death, glial cell activation, neuroinflammation, and neurovascular dysfunction, in addition to elevated levels of amyloid β (Aβ) and tau phosphorylation. Oxidative stress and the oxidative stress-sensitive TRPM2 channel play important roles in mediating multiple molecular and cellular alterations that underpin AD-related cognitive dysfunction. Documented evidence suggests critical engagement of oxidative stress and TRPM2 channel activation in various PM2.5-induced cellular effects. Here we discuss recent studies that favor causative relationships of PM2.5 exposure to increased AD prevalence and AD- and age-related pathologies, and raise the perspective on the roles of oxidative stress and the TRPM2 channel in mediating PM2.5-induced predisposition to AD and age-related brain damage.
    Matched MeSH terms: Cell Death
  5. Toxicity assessment of reduced graphene oxide and titanium dioxide nanomaterials on gram-positive and gram-negative bacteria under normal laboratory lighting condition
    Ahmad NS, Abdullah N, Yasin FM
    Toxicol Rep, 2020;7:693-699.
    PMID: 32528857 DOI: 10.1016/j.toxrep.2020.04.015
    Toxicity effect of reduced graphene oxide (rGO) and titanium dioxide (TiO2) nanomaterials (NMs) on Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) bacteria was assessed. For both strains, study demonstrated that the toxicity was time and concentration dependent which led to reduction in growth rate and cell death. Upon NMs exposure, an instantaneous cell death in E. coli culture was observed. This is in contrast with B. subtilis, in which the culture growth remained in the log phase; however their growth rate constant,

    μ
    g

    was reduced by ∼70%. The discrepancy between E. coli and B. subtilis was due to strain-specific response upon contact with NMs. TEM, SEM and EDX analysis revealed direct physical surface-surface interaction, as evidence from the adherence of NMs on the cell surface.
    Matched MeSH terms: Cell Death
  6. Antibacterial and cytotoxic effect of honey mediated copper nanoparticles synthesized using ultrasonic assistance
    Ismail NA, Shameli K, Wong MM, Teow SY, Chew J, Sukri SNAM
    Mater Sci Eng C Mater Biol Appl, 2019 Nov;104:109899.
    PMID: 31499959 DOI: 10.1016/j.msec.2019.109899
    In this study, a comparative study of effect using honey on copper nanoparticles (Cu-NPs) via simple, environmentally friendly process and inexpensive route was reported. Honey and ascorbic acid act as stabilizing and reducing agents with the assistance of sonochemical method. The products were characterized using UV-visible (UV-vis) spectroscopy, X-Ray Diffraction (XRD), High-Resolution Transmission Electron Microscopy (HRTEM), Field-Emission Scanning Electron Microscopy (FESEM) and Fourier Transform Infrared (FTIR) spectroscopy. The reddish brown colour demonstrated the formation of Cu-NPs and UV-visible proved the plasmon resonance of Cu-NPs. XRD also confirmed a highly pure Cu-NPs obtained with absence of copper oxide in which the structure is crystalline. The spherical size of the Cu-NPs was acquire in the presence of honey which is 3.68 ± 0.78 nm with narrow particle distribution. The antibacterial activity was seen against gram-positive and gram-negative bacteria which are Enterococcus faecalis (E. faecalis) and Escherichia coli (E. coli). At higher concentration of Cu-NPs, they were more effective in killing both bacteria. The Cu-NPs without and with honey exhibited toxicities toward normal and cancerous cells. However, Cu-NPs without honey showed more potent killing activity against normal and cancer cells.
    Matched MeSH terms: Cell Death/drug effects
  7. Metabolic role of fatty acid binding protein 7 in mediating triple-negative breast cancer cell death via PPAR-α signaling
    Kwong SC, Jamil AHA, Rhodes A, Taib NA, Chung I
    J Lipid Res, 2019 11;60(11):1807-1817.
    PMID: 31484694 DOI: 10.1194/jlr.M092379
    Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, partly due to the lack of targeted therapy available. Cancer cells heavily reprogram their metabolism and acquire metabolic plasticity to satisfy the high-energy demand due to uncontrolled proliferation. Accumulating evidence shows that deregulated lipid metabolism affects cancer cell survival, and therefore we sought to understand the function of fatty acid binding protein 7 (FABP7), which is expressed predominantly in TNBC tissues. As FABP7 was not detected in the TNBC cell lines tested, Hs578T and MDA-MB-231 cells were transduced with lentiviral particles containing either FABP7 open reading frame or red fluorescent protein. During serum starvation, when lipids were significantly reduced, FABP7 decreased the viability of Hs578T, but not of MDA-MB-231, cells. FABP7-overexpressing Hs578T (Hs-FABP7) cells failed to efficiently utilize other available bioenergetic substrates such as glucose to sustain ATP production, which led to S/G2 phase arrest and cell death. We further showed that this metabolic phenotype was mediated by PPAR-α signaling, despite the lack of fatty acids in culture media, as Hs-FABP7 cells attempted to survive. This study provides imperative evidence of metabolic vulnerabilities driven by FABP7 via PPAR-α signaling.
    Matched MeSH terms: Cell Death
  8. α1-Acid Glycoprotein Has the Potential to Serve as a Biomimetic Drug Delivery Carrier for Anticancer Agents
    Matsusaka K, Ishima Y, Maeda H, Kinoshita R, Ichimizu S, Taguchi K, et al.
    J Pharm Sci, 2019 11;108(11):3592-3598.
    PMID: 31288036 DOI: 10.1016/j.xphs.2019.07.002
    Nanosize plasma proteins could be used as a biomimetic drug delivery system (DDS) for cancer treatment when loaded with anticancer drugs based on the fact that plasma proteins can serve as a source of nutrients for cancer cells. This prompted us to investigate the potential of α1-acid glycoprotein (AGP) for this role because it is a nanosize plasma protein and binds a variety of anticancer agents. Pharmacokinetic analyses indicated that AGP is distributed more extensively in tumor tissue than human serum albumin, which was already established as a cancer DDS carrier. AGP is possibly being incorporated into tumor cells via endocytosis pathways. Moreover, a synthetic AGP-derived peptide which possesses a high ability to form an α-helix, as deduced from the primary structure of AGP, was also taken up by the tumor cells. AGP loaded with anticancer agents, such as paclitaxel or nitric oxide, efficiently induced tumor cell death. These results suggest that AGP has the potential to be a novel DDS carrier for anticancer agents.
    Matched MeSH terms: Cell Death/drug effects
  9. Induction of ROS‑mediated cell death and activation of the JNK pathway by a sulfonamide derivative
    Ahmad R, Vaali-Mohammed MA, Elwatidy M, Al-Obeed O, Al-Khayal K, Eldehna WM, et al.
    Int J Mol Med, 2019 Jul 23.
    PMID: 31364730 DOI: 10.3892/ijmm.2019.4284
    The emergence of colorectal cancer in developed nations can be attributed to dietary habits, smoking, a sedentary lifestyle and obesity. Several treatment regimens are available for primary and metastatic colorectal cancer; however, these treatment options have had limited impact on cure and disease‑free survival, and novel agents need to be developed for treating colorectal cancer. Thus, the objective of this study was to explore the anticancer mechanism of a benzo(1,3)dioxol‑based derivative of sulfonamide. The compound's inhibitory effect on cell proliferation was determined using the MTT assay and the xCelligence RTDP machine. Alternations in the expression of Bcl‑2 and inhibitor of apoptosis protein families were detected by western blotting. Apoptotic marker protein expression, including cytochrome c and cleaved poly(ADP‑ribose)polymerase was measured in the cytosolic extract of cells. Apoptosis and necrosis were detected by flow cytometry and immunofluorescence. Reactive oxygen species (ROS), and activation of caspase‑3 and caspase‑7 were measured using flow cytometry. Activation of the JNK pathway was detected by western blotting. We investigated the molecular mechanism of action of the sulfonamide derivative on colorectal cancer cells and found that the compound possesses a potent anticancer effect, which is primarily exerted by inducing apoptosis and necrosis. Interestingly, this compound exhibited little antiproliferative effect against the normal colonic epithelial cell line FHC. Furthermore, our results showed that the compound could significantly increase ROS production. Apoptosis induction could be attenuated by the free oxygen radical scavenger N‑acetyl cysteine (NAC), indicating that the antiproliferative effect of this compound on colorectal cancer cells is at least partially dependent on the redox balance. In addition, JNK signaling was activated by treatment with this derivative, which led to the induction of apoptosis. On the contrary, a JNK inhibitor could suppress the cell death induced by this compound. Our findings thus suggested a novel anticancer mechanism of a benzo(1,3)dioxol‑based derivative of sulfonamide for colorectal cancer cells and may have therapeutic potential for the treatment of colorectal cancer; however, further investigation is required.
    Matched MeSH terms: Cell Death
  10. Preparation of letrozole dispersed pHEMA/AAm-g-LDPE drug release system: In-vitro release kinetics for the treatment of endometriosis
    Siddiqa AJ, Shrivastava NK, Ali Mohsin ME, Abidi MH, Shaikh TA, El-Meligy MA
    Colloids Surf B Biointerfaces, 2019 Jul 01;179:445-452.
    PMID: 31005739 DOI: 10.1016/j.colsurfb.2019.04.014
    This paper focuses on the development of a drug delivery system for systemically controlled release of a poorly soluble drug, letrozole. The work meticulously describes the preparation and characterizations of 2-hydroxyethyl methacrylate (HEMA) polymerization onto hydrophilic acrylamide grafted low-density polyethylene (AAm-g-LDPE) surface for targeted drug release system. The surface morphology and thickness measurement of coated pHEMA layer were measured using scanning electron microscopy (SEM). The swelling study was done in deionized (DI) water and simulated uterine fluid (SUF, pH = 7.6). In vitro release of letrozole from the system was performed in SUF. Further, the release kinetics of letrozole from the system was studied using different mathematical models. The results, suggest that the rate of drug release can be altered by varying the concentrations of cross-linker in pHEMA. The optimized sample released 72% drug at the end of 72 h of measurement.
    Matched MeSH terms: Cell Death/drug effects
  11. A computational model to investigate the influence of electrode lengths on the single probe bipolar radiofrequency ablation of the liver
    Cheong JKK, Yap S, Ooi ET, Ooi EH
    Comput Methods Programs Biomed, 2019 Jul;176:17-32.
    PMID: 31200904 DOI: 10.1016/j.cmpb.2019.04.028
    BACKGROUND AND OBJECTIVES: Recently, there have been calls for RFA to be implemented in the bipolar mode for cancer treatment due to the benefits it offers over the monopolar mode. These include the ability to prevent skin burns at the grounding pad and to avoid tumour track seeding. The usage of bipolar RFA in clinical practice remains uncommon however, as not many research studies have been carried out on bipolar RFA. As such, there is still uncertainty in understanding the effects of the different RF probe configurations on the treatment outcome of RFA. This paper demonstrates that the electrode lengths have a strong influence on the mechanics of bipolar RFA. The information obtained here may lead to further optimization of the system for subsequent uses in the hospitals.

    METHODS: A 2D model in the axisymmetric coordinates was developed to simulate the electro-thermophysiological responses of the tissue during a single probe bipolar RFA. Two different probe configurations were considered, namely the configuration where the active electrode is longer than the ground and the configuration where the ground electrode is longer than the active. The mathematical model was first verified with an existing experimental study found in the literature.

    RESULTS: Results from the simulations showed that heating is confined only to the region around the shorter electrode, regardless of whether the shorter electrode is the active or the ground. Consequently, thermal coagulation also occurs in the region surrounding the shorter electrode. This opened up the possibility for a better customized treatment through the development of RF probes with adjustable electrode lengths.

    CONCLUSIONS: The electrode length was found to play a significant role on the outcome of single probe bipolar RFA. In particular, the length of the shorter electrode becomes the limiting factor that influences the mechanics of single probe bipolar RFA. Results from this study can be used to further develop and optimize bipolar RFA as an effective and reliable cancer treatment technique.

    Matched MeSH terms: Cell Death
  12. Bactericidal and cytotoxic activity of a diarylheptanoid (etlingerin) isolated from a ginger (Etlingera pubescens) endemic to Borneo
    Daniel-Jambun D, Ong KS, Lim YY, Tan JBL, Yap SW, Lee SM
    J Appl Microbiol, 2019 Jul;127(1):59-67.
    PMID: 31006174 DOI: 10.1111/jam.14287
    AIMS: The aim of this study was to investigate the antimicrobial activities of Etlingera pubescens, and to isolate and identify the antimicrobial compound.

    METHODS AND RESULTS: The crude extracts of E. pubescens were obtained through methanol extraction, and evaluated for antimicrobial activities. From this extract, 1,7-bis(3,4-dihydroxyphenyl)heptan-3-yl acetate (etlingerin) was isolated. When compared to curcumin (a compound with a similar chemical structure), etlingerin showed twofold lower minimum inhibitory concentration values while also being bactericidal. Through time kill assay, etlingerin showed rapid killing effects (as fast as 60 min) against the Gram-positive bacteria (Staphylococcus aureus ATCC 43300 and Bacillus subtilis ATCC 8188). Further assessment revealed that etlingerin caused leakage of intracellular materials, therefore suggesting alteration in membrane permeability as its antimicrobial mechanism. Cytotoxicity study demonstrated that etlingerin exhibited approximately 5- to 12-fold higher IC50 values against several cell lines, as compared to curcumin.

    CONCLUSIONS: Etlingerin isolated from E. pubescens showed better antibacterial and cytotoxic activities when compared to curcumin. Etlingerin could be safe for human use, though further cytotoxicity study using animal models is needed.

    SIGNIFICANCE AND IMPACT OF THE STUDY: Etlingerin has a potential to be used in treating bacterial infections due to its good antimicrobial activity, while having potentially low cytotoxicity.

    Matched MeSH terms: Cell Death/drug effects
  13. Proteomic analysis of flavokawain C-induced cell death in HCT 116 colon carcinoma cell line
    Phang CW, Gandah NA, Abd Malek SN, Karsani SA
    Eur J Pharmacol, 2019 Jun 15;853:388-399.
    PMID: 31014923 DOI: 10.1016/j.ejphar.2019.04.032
    Flavokawain C (FKC), a naturally occurring chalcone, has previously been shown to inhibit the growth of colon carcinoma HCT 116 cells through induction of apoptosis and cell cycle arrest. However, the possible underlying mechanisms of cell death as a response to FKC treatment remains unclear. In this study, we performed proteomic analysis of HCT 116 cells treated with FKC to identify proteins that change in abundance. This was followed by bioinformatic analysis to predict possible associated molecular targets or pathways involved in the observed effects of FKC. A total of 35 proteins that changed in abundance (17 increased and 18 decreased) were identified through two-dimensional gel electrophoresis followed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF/TOF MS). Using the Ingenuity Pathway Analysis (IPA), these proteins were predicted to be involved in cell death and survival, cell cycle, cellular growth and proliferation, protein synthesis, post-translational modification and amino acid metabolism by. Further analysis of the transcript levels of selected proteins using qPCR showed that some of the genes exhibited similar change of profile to that of the proteins'. Our results have provided novel insights into the potential molecular mechanisms underlying FKC-induced apoptosis or cell death in colon cancer cells.
    Matched MeSH terms: Cell Death/drug effects
  14. In-vitro phagocytosis and intracellular killing of Pasteurella multocida B:2 by phagocytic cells of buffaloes
    Puspitasari Y, Annas S, Adza-Rina MN, Zamri-Saad M
    Microb Pathog, 2019 Jun;131:170-174.
    PMID: 30978429 DOI: 10.1016/j.micpath.2019.04.012
    Pasteurella multocida B:2 is a Gram-negative organism causing haemorrhagic septicaemia (HS) in buffaloes. It causes severe pulmonary infection, leading to infiltration of numerous macrophages and neutrophils. Despite the inflammatory response, buffaloes succumb to HS. This study aims to evaluate the in-vitro efficacy of macrophages and neutrophils of buffalo following exposure to P. multocida B:2. In-vitro infections were done using 107 cfu/ml of P. multocida B:2 for Group 1, Escherichia coli for Group 2 and Mannhaemia haemolytica A:2 for Group 3 cells. The inoculated cell cultures were harvested at 0, 30, 60 and 120 min post-exposure and the phagocytic, killing and cell death rates were determined. Both phagocytosis and killing rates of all bacteria increased over time. Phagocytosis involved between 71% and 73% neutrophils and between 60% and 64% macrophages at 120 min. Killing rate of all bacteria involved between 76% and 79% for neutrophils and between 70% and 74% for macrophages at 120 min. Death rate of neutrophils ranged between 67% in Group 3, and 88% in Group 1 at 120 min, significantly (p  0.05) than Group 2. Similar pattern was observed for death rate of macrophages. The phagocytosis and killing rates of P. multocida B:2 were similar to other bacterial species used in this study but more neutrophils and macrophages were dead following infection by P. multocida B:2 than M. haemolytica A:2.
    Matched MeSH terms: Cell Death
  15. Functionalizing the surface of hydroxyapatite drug carrier with carboxylic acid groups to modulate the loading and release of curcumin nanoparticles
    Lee WH, Loo CY, Rohanizadeh R
    Mater Sci Eng C Mater Biol Appl, 2019 Jun;99:929-939.
    PMID: 30889767 DOI: 10.1016/j.msec.2019.02.030
    This study has evaluated the effect of functionalizing surface charges of hydroxyapatite on the modulation of loading and release of curcumin nanoparticles. The increase in loading and release of curcumin nanoparticles indirectly translates to enhanced anti-cancer effect. Owing to the hydrophobic characteristics of curcumin which have resulted in low bioavailability in cancer cells, the engineering curcumin into nanoparticles is therefore a viable solution to overcomes its limitation. In order to maintain a sustained release profile of curcumin nanoparticles, curcumin nanoparticles were loaded (Cur-NPs) onto hydroxyapatite (HA) via physical adsorption. To regulate the adsorption capacity of Cur-NPs onto HA, we functionalized HA with different carboxylic acids (lactic acid, tartaric acid and citric acid). The presence of carboxylic groups on HA significantly affected the binding and the release profile of Cur-NPs. The effects of Cur-NPs loaded HA were evaluated on breast cancer cell line (MCF-7), which included cell proliferation, cellular uptake of Cur-NPs, apoptosis and cell cycle analysis. The results showed that carboxylic acid-functionalized HA demonstrated higher anti-proliferating activity and time dependent cytoplasmic uptake of Cur-NPs in MCF-7 cells compared to unmodified HA. In addition, Cur-NPs loaded on functionalized HA induced higher apoptosis and cell cycle arrest in MCF-7 cells compared to unmodified HA. The present study indicates that the delivery of Cur-NPs to breast cancer using carboxylic acid-functionalized HA carrier could improve their anti-cancer activities.
    Matched MeSH terms: Cell Death/drug effects
  16. Fulltext Strontium Sulfite: A New pH-Responsive Inorganic Nanocarrier to Deliver Therapeutic siRNAs to Cancer Cells
    Karim ME, Shetty J, Islam RA, Kaiser A, Bakhtiar A, Chowdhury EH
    Pharmaceutics, 2019 Feb 20;11(2).
    PMID: 30791612 DOI: 10.3390/pharmaceutics11020089
    Inorganic nanoparticles hold great potential in the area of precision medicine, particularly for treating cancer owing to their unique physicochemical properties, biocompatibility and improved pharmacokinetics properties compared to their organic counterparts. Here we introduce strontium sulfite nanoparticles as new pH-responsive inorganic nanocarriers for efficient transport of siRNAs into breast cancer cells. We employed the simplest nanoprecipitation method to generate the strontium sulfite nanoparticles (SSNs) and demonstrated the dramatic roles of NaCl and d-glucose in particle growth stabilization in order to produce even smaller nanosize particles (Na-Glc-SSN) with high affinity towards negatively charged siRNA, enabling it to efficiently enter the cancer cells. Moreover, the nanoparticles were found to be degraded with a small drop in pH, suggesting their potential capability to undergo rapid dissolution at endosomal pH so as to release the payload. While these particles were found to be nontoxic to the cells, they showed higher potency in facilitating cancer cell death through intracellular delivery and release of oncogene-specific siRNAs targeting ros1 and egfr1 mRNA transcripts, than the strontium sulfite particles prepared in absence of NaCl and d-glucose, as confirmed by growth inhibition assay. The mouse plasma binding analysis by Q-TOF LC-MS/MS demonstrated less protein binding to smaller particles of Na-Glc-SSNs. The biodistribution studies of the particles after 4 h of treatment showed Na-Glc-SSNs had less off-target distribution than SSNs, and after 24 h, all siRNAs were cleared from all major organs except the tumors. ROS1 siRNA with its potential therapeutic role in treating 4T1-induced breast tumor was selected for subsequent in vivo tumor regression study, revealing that ROS1 siRNA-loaded SSNs exerted more significant anti-tumor effects than Na-Glc-SSNs carrying the same siRNA following intravenous administration, without any systemic toxicity. Thus, strontium sulfite emerged as a powerful siRNA delivery tool with potential applications in cancer gene therapy.
    Matched MeSH terms: Cell Death
  17. Fulltext Arctium lappa L. root extract induces cell death via mitochondrial-mediated caspase-dependent apoptosis in Jurkat human leukemic T cells
    Gurunanselage Don RAS, Yap MKK
    Biomed Pharmacother, 2019 Feb;110:918-929.
    PMID: 30572196 DOI: 10.1016/j.biopha.2018.12.023
    Arctium lappa L. is a perennial herb traditionally consumed to improve well-being. It has been widely reported for its antioxidant properties; however, very little is known for its exact mechanisms underlying the anticancer activity. This study aimed to investigate the mechanisms of anticancer action for different A. lappa root extracts. Arctium lappa root was extracted with ethanol, hexane and ethyl acetate, then examined for in vitro anticancer activity against cancerous HeLa, MCF-7, Jurkat cell lines and non-cancerous 3T3 cell lines. Induction of apoptosis was determined by cellular morphological changes, mitochondrial membrane potential (ΔΨm), caspase-3/7 activity and DNA fragmentation. The active compounds present in the most potent root extracts were identified by LC-ESI-MS. Among all the extracts, ethyl acetate root extract has the highest potency with IC50 of 102.2 ± 42.4 μg/ml, followed by ethanolic root extract in Jurkat T cells, at 24 h. None of the extracts were cytotoxic against 3T3 cells, suggesting that the extracts were selective against cancerous cells only. Both ethyl acetate and ethanolic root extracts exhibited significant morphological changes in Jurkat T cells, including the detachment from adjacent cells, appearance of apoptotic bodies and cells shrinkage. The extracts treated cells also displayed an increase in caspase-3/7 activity and alteration in mitochondrial membrane potential. Only ethyl acetate root extract at IC50 induced DNA fragmentation in Jurkat T cells. LC-ESI-MS analysis of the extract revealed the presence of 8 compounds, of which only 6 compounds with various biological activities reported. These findings suggest that the ethyl acetate extract of A. lappa had strong anticancer potential and induced intrinsic apoptosis via loss of ΔΨm and activation of caspase-3/7 This study can provide new insight to the discovery of new promising lead compound in chemopreventive and chemotherapeutic strategies.
    Matched MeSH terms: Cell Death/drug effects; Cell Death/physiology
  18. Fulltext Involvement of the uridine cytidine kinase 2 enzyme in cancer cell death: A molecular crosstalk between the enzyme and cellular apoptosis induction
    Malami I, Abdul AB
    Biomed Pharmacother, 2019 Jan;109:1506-1510.
    PMID: 30551402 DOI: 10.1016/j.biopha.2018.10.200
    Apoptosis is a series of molecular signalling regulating normal cellular growth and development. Cells resistance to apoptosis, however, leads to uncontrolled proliferation. Research involving cancer cell death is one of the most important targeted areas in the discovery of novel anticancer therapy. There are several biochemical pathways that are liked towards cancer cell death of which, uridine-cytidine kinase 2 (UCK2) was recently linked to cell apoptosis induction. UCK2 is responsible for the phosphorylation of uridine and cytidine to their corresponding monophosphate in a salvage pathway of pyrimidine nucleotides biosynthesis. Cytotoxic ribonucleoside analogues that target UCK2 enzyme activity are currently being investigated in clinical trials useful for cancer treatment. Whilst findings have clearly shown that these antimetabolites inhibit cancer development in clinical settings, they have yet to establish linking cytotoxic nucleoside analogues to cancer cell death. In this present review, we propose the probable molecular crosstalk involving UCK2 protein and cancer cell death through cell cycle arrest and triggering of apoptosis involving proteins, MDM2 and the subsequent activation of p53.
    Matched MeSH terms: Cell Death/physiology*
  19. Studies on the interaction of mononuclear metal(II) complexes of amino‑naphthoquinone with bio-macromolecules
    Kosiha A, Lo KM, Parthiban C, Elango KP
    Mater Sci Eng C Mater Biol Appl, 2019 Jan 01;94:778-787.
    PMID: 30423764 DOI: 10.1016/j.msec.2018.10.021
    Three metal(II) complexes [CoLCl2], [CuLCl2] and [ZnL2Cl2] {L = 2‑chloro‑3‑((3‑dimethylamino)propylamino)naphthalene‑1,4‑dione} have been synthesized and characterized using analytical, thermal and spectral techniques (FT-IR, UV-Vis, ESR and ESI-MS). The structure of the L has been confirmed by single crystal XRD study. The complexes show good binding propensity to bovine serum albumin (BSA) having relatively higher binding constant values (104 M-1) than the ligand. Fluorescence spectral studies indicate that [CoLCl2] binds relatively stronger with CT DNA through intercalative mode, exhibiting higher binding constant (2.22 × 105 M-1). Agarose gel electrophoresis run on plasmid DNA (pUC18) prove that all the complexes showed efficient DNA cleavage via hydroxyl radical mechanism. The complexes were identified as potent anticancer agents against two human cancer cell lines (MCF7 and A549) by comparing with cisplatin. Co(II) complex demonstrated greater cytotoxicity against MCF7 and A549 cells with IC50 values at 19 and 22 μM, respectively.
    Matched MeSH terms: Cell Death
  20. Fulltext Chlamydia and Its Many Ways of Escaping the Host Immune System
    Wong WF, Chambers JP, Gupta R, Arulanandam BP
    J Pathog, 2019;2019:8604958.
    PMID: 31467721 DOI: 10.1155/2019/8604958
    The increasing number of new cases of Chlamydia infection worldwide may be attributed to the pathogen's ability to evade various host immune responses. Summarized here are means of evasion utilized by Chlamydia enabling survival in a hostile host environment. The pathogen's persistence involves a myriad of molecular interactions manifested in a variety of ways, e.g., formation of membranous intracytoplasmic inclusions and cytokine-induced amino acid synthesis, paralysis of phagocytic neutrophils, evasion of phagocytosis, inhibition of host cell apoptosis, suppression of antigen presentation, and induced expression of a check point inhibitor of programmed host cell death. Future studies could focus on the targeting of these molecules associated with immune evasion, thus limiting the spread and tissue damage caused by this pathogen.
    Matched MeSH terms: Cell Death
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