Displaying publications 41 - 60 of 190 in total

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  1. Protective Role of Natural Products in Cisplatin-Induced Nephrotoxicity
    Ridzuan NRA, Rashid NA, Othman F, Budin SB, Hussan F, Teoh SL
    Mini Rev Med Chem, 2019;19(14):1134-1143.
    PMID: 30894108 DOI: 10.2174/1389557519666190320124438
    Cisplatin is a widely used antineoplastic agent for the treatment of metastatic tumors, advanced bladder cancer and many other solid tumors. However, at higher doses, toxicities such as nephrotoxicity may appear. Cisplatin leads to DNA damage and subsequently renal cell death. Besides that, oxidative stress is also implicated as one of the main causes of nephrotoxicity. Several studies showed that numerous natural products: ginseng, curcumin, licorice, honey and pomegranate were able to reduce the oxidative stress by restoring the levels of antioxidant enzymes and also at the same time act as an anti-inflammatory agent. Furthermore, pre-treatment with vitamin supplementation, such as vitamin C, E and riboflavin markedly decreased serum urea and increased the levels of antioxidant enzymes in the kidney even after cisplatin induction in cancer patients. These natural products possess potent antioxidant and anti-inflammatory medicinal properties, and they can be safely used as a supplementary regime or combination therapy against cisplatin-induced nephrotoxicity. The present review focused on the protective role of a few natural products which is widely used in folk medicines in cisplatin-induced nephrotoxicity.
    Matched MeSH terms: Cell Death
  2. Fulltext Programmed cell death-ligand, thymidylate synthase and deleted in colorectal carcinoma biomarkers in colorectal carcinoma
    Fauzah Abd Ghani, Reena Rehavu Zin, Maha Abdullah, Norhafizah Mohtarrudin, Ebenyi Emeka Onwe
    Malaysian Journal of Medicine and Health Sciences, 2019;15(108):16-16.
    MyJurnal
    Introduction: It is well known that cancer cells evade the immune system with the help of programmed cell death protein 1 (PD-L1) molecule to remain undetected, causing abnormal proliferation of T-cells. PD-L1 expression on the surface of neoplastic cells inhibits cytotoxic T-cell responses which lead to negative regulation of cytokines and proliferation of T-cells. The deleted in colorectal cancer (DCC) gene belongs to the immunoglobulin superfamily. It is a candidate of the tumour suppressor gene by regulating apoptosis. DCC assessment gives an insight into progno-sis in patients with advanced stages of CRC. Thymidylate synthase (TYMS) is a highly conserved enzyme involved in DNA synthesis. TYMS has been an important target for cancer chemotherapy because of its central, rate-limiting role in de novo synthesis of thymidylate. Expression of PD-L1, TYMS and DCC has been demonstrated to confer a prognostic value in CRC but none have been completely validated for patient care. This study aimed to determine the prognostic and predictive potential of PD-L1, TYMS, and DCC biomarkers in CRC. Methods: The expression of these biomarkers was evaluated immunohistochemically in 91 formalin-fixed paraffin-embedded (FFPE) archival tumour samples from patients that underwent surgical resection. Results: There was high expression of DCC in most cases; 84.6% (77/91). TYMS expression at a high level score was 46.2% (42/91) and at low level was 53.8% (49/91). Majority of cases had low PD-L1 expression in 93.4% (86/91) cases and high expression was detected in 6.6% (6/94) of cases. In addition, there was a significant association between TYMS expression with gender (P < 0.05) with distribution of TYMS expression detected at high level was 76.2% in male and 23.8% in female. The Kaplan-Meier survival plot showed mean overall survival in patients with PD-L1 with high expression to be 22 months, which pre-dicts better survival. TYMS low expression showed mean overall survival of 90 which also indicated better survival. DCC high expression showed mean overall survival of 90 which indicated better survival. The correlation between the biomarkers and overall survival were not statistically significant. Conclusion: The results from this study suggest that PD-L1, TYMS and DCC expression could be used as biomarkers to predict treatment outcome in CRC. PD-L1 overexpression predicts patients who could benefit from anti-PD-1 and anti-PD-L1 immunotherapy whilst TYMS low expression predicts patients who could benefit from 5-fluorouracil therapy. DCC high expression tumours predicts a better prognosis and overall survival compared to DCC-negative tumours in advanced CRC.
    Matched MeSH terms: Programmed Cell Death 1 Receptor
  3. 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
  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. Prediction of colorectal cancer driver genes from patients’ genome data
    Muhammad-iqmal Abdullah, Nor Azlan Nor Muhammad
    Sains Malaysiana, 2018;47:3095-3105.
    Colorectal cancer refers to the cancer that occurs in the colon and rectum. It has been established as the third most
    common cancer and the forth one in causing worldwide mortality. Cancer caused by the mutation of several genes that
    usually involved in the regulation of cell proliferation, growth and cell death. The mutation that leads to abnormal
    function of genes, either in enabling the genes to gain or loss of function was termed as driver mutation and the genes
    with driver mutation ability was termed as driver genes. The identification of driver genes provides insight on mechanistic
    process of cancer development where this information can be used to further understand their mode of action for causing
    dysregulation in signaling pathways. In this study, two bioinformatic tools, i.e. CGI and iCAGES were used to predict
    potential driver genes from the genome of eight colorectal cancer patients with annotated variants datasets. 44 unique
    driver genes and 21 pathways have been identified; such as p53 signaling, PI3K-AKT, Endocrine resistance, MAPK and
    cell cycle pathways. The identification of these pathways can lead to the identification of potential drugs targeting these
    pathways.
    Matched MeSH terms: Cell Death
  6. Fulltext Pre-clinical evaluation of novel mucoadhesive bilayer patches for local delivery of clobetasol-17-propionate to the oral mucosa
    Colley HE, Said Z, Santocildes-Romero ME, Baker SR, D'Apice K, Hansen J, et al.
    Biomaterials, 2018 09;178:134-146.
    PMID: 29929183 DOI: 10.1016/j.biomaterials.2018.06.009
    Oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS) are chronic inflammatory conditions often characterised by erosive and/or painful oral lesions that have a considerable impact on quality of life. Current treatment often necessitates the use of steroids in the form of mouthwashes, creams or ointments, but these are often ineffective due to inadequate drug contact times with the lesion. Here we evaluate the performance of novel mucoadhesive patches for targeted drug delivery. Electrospun polymeric mucoadhesive patches were produced and characterised for their physical properties and cytotoxicity before evaluation of residence time and acceptability in a human feasibility study. Clobetasol-17-propionate incorporated into the patches was released in a sustained manner in both tissue-engineered oral mucosa and ex vivo porcine mucosa. Clobetasol-17 propionate-loaded patches were further evaluated for residence time and drug release in an in vivo animal model and demonstrated prolonged adhesion and drug release at therapeutic-relevant doses and time points. These data show that electrospun patches are adherent to mucosal tissue without causing tissue damage, and can be successfully loaded with and release clinically active drugs. These patches hold great promise for the treatment of oral conditions such as OLP and RAS, and potentially many other oral lesions.
    Matched MeSH terms: Cell Death/drug effects
  7. Potential of Gold Candidates against Human Colon Cancer
    Abbasi M, Yaqoob M, Haque RA, Iqbal MA
    Mini Rev Med Chem, 2021;21(1):69-78.
    PMID: 32767935 DOI: 10.2174/1389557520666200807130721
    Development of novel metallodrugs with pharmacological profile plays a significant role in modern medicinal chemistry and drug design. Metal complexes have shown remarkable clinical results in current cancer therapy. Gold complexes have attained attention due to their high antiproliferative potential. Gold-based drugs are used for the treatment of rheumatoid arthritis. Gold-containing compounds with selective and specific targets are capable to assuage the symptoms of a range of human diseases. Gold (I) species with labile ligands (such as Cl in TEPAuCl) interact with isolated DNA; therefore, this biomolecule has been considered as a target for gold drugs. Gold (I) has a high affinity towards sulfur and selenium. Due to this, gold (I) drugs readily interact with cysteine or selenocysteine residue of the enzyme to form protein-gold(I) thiolate or protein-gold (I) selenolate complexes that lead to inhibition of the enzyme activity. Au(III) compounds due to their square-planner geometriesthe same as found in cisplatin, represent a good source for the development of anti-tumor agents. This article aims to review the most important applications of gold products in the treatment of human colon cancer and to analyze the complex interplay between gold and the human body.
    Matched MeSH terms: Cell Death/drug effects
  8. Fulltext Potential effects of chrysin on MDA-MB-231 cells
    Hong TB, Rahumatullah A, Yogarajah T, Ahmad M, Yin KB
    Int J Mol Sci, 2010;11(3):1057-69.
    PMID: 20479999 DOI: 10.3390/ijms11031057
    This study aims to elucidate the effects of chrysin on human ER-negative breast cancer cell line, MDA-MB-231. The study demonstrated that treatment of MDA-MB-231 cells with 20 microM chysin for 48 h significantly inhibited the growth of MDA-MB-231 cells and induced cytoplasmic lipid accumulation in the cells, but that the observed of cell death was not caused by apoptosis. The expression of PPARalpha mRNA in chrysin-treated MDA-MB-231 cells was significantly increased, which was likely associated to the proliferation of the cells post chrysin treatment.
    Matched MeSH terms: Cell Death/drug effects
  9. Fulltext Potential activity of fevicordin-A from Phaleria macrocarpa (Scheff) Boerl. seeds as estrogen receptor antagonist based on cytotoxicity and molecular modelling studies
    Muchtaridi M, Yusuf M, Diantini A, Choi SB, Al-Najjar BO, Manurung JV, et al.
    Int J Mol Sci, 2014 Apr 25;15(5):7225-49.
    PMID: 24776765 DOI: 10.3390/ijms15057225
    Fevicordin-A (FevA) isolated from Phaleria macrocarpa (Scheff) Boerl. seeds was evaluated for its potential anticancer activity by in vitro and in silico approaches. Cytotoxicity studies indicated that FevA was selective against cell lines of human breast adenocarcinoma (MCF-7) with an IC50 value of 6.4 µM. At 11.2 µM, FevA resulted in 76.8% cell death of T-47D human breast cancer cell lines. Critical pharmacophore features amongst human Estrogen Receptor-α (hERα) antagonists were conserved in FevA with regard to a hypothesis that they could make notable contributions to its pharmacological activity. The binding stability as well as the dynamic behavior of FevA towards the hERα receptor in agonist and antagonist binding sites were probed using molecular dynamics (MD) simulation approach. Analysis of MD simulation suggested that the tail of FevA was accountable for the repulsion of the C-terminal of Helix-11 (H11) in both agonist and antagonist receptor forms. The flexibility of loop-534 indicated the ability to disrupt the hydrogen bond zipper network between H3 and H11 in hERα. In addition, MM/GBSA calculation from the molecular dynamic simulations also revealed a stronger binding affinity of FevA in antagonistic action as compared to that of agonistic action. Collectively, both the experimental and computational results indicated that FevA has potential as a candidate for an anticancer agent, which is worth promoting for further preclinical evaluation.
    Matched MeSH terms: Cell Death/drug effects
  10. Fulltext Phyto-Mediated Photo Catalysed Green Synthesis of Silver Nanoparticles Using Durio Zibethinus Seed Extract: Antimicrobial and Cytotoxic Activity and Photocatalytic Applications
    Sumitha S, Vasanthi S, Shalini S, Chinni SV, Gopinath SCB, Anbu P, et al.
    Molecules, 2018 Dec 13;23(12).
    PMID: 30551671 DOI: 10.3390/molecules23123311
    In the present study, we have developed a green approach for the synthesis of silver nanoparticles (DSAgNPs) using aqueous extract of Durio zibethinus seed and determined its antibacterial, photocatalytic and cytotoxic effects. Surface plasmon resonance confirmed the formation of DSAgNPs with a maximum absorbance (λmax) of 420 nm. SEM and TEM images revealed DSAgNPs were spherical and rod shaped, with a size range of 20 nm and 75 nm. The zeta potential was found to be -15.41 mV. XRD and EDX analyses confirmed the nature and presence of Ag and AgCl. DSAgNPs showed considerable antibacterial activity, exhibited better cytotoxicity against brine shrimp, and shown better photocatalytic activity against methylene blue. Based on the present research work, it can be concluded that DSAgNPs could be used in the field of water treatment, pharmaceuticals, biomedicine, biosensor and nanotechnology in near future.
    Matched MeSH terms: Cell Death/drug effects
  11. Fulltext Phylattrin, a new cytotoxic xanthone from Calophyllum soulattri
    Mah SH, Ee GC, Teh SS, Rahmani M, Lim YM, Go R
    Molecules, 2012 Jul 10;17(7):8303-11.
    PMID: 22781442 DOI: 10.3390/molecules17078303
    Our continuing studies on secondary metabolites from the stem bark of Calophyllum soulattri has led to the isolation of another new diprenylated xanthone, phylattrin (1), in addition to five other xanthones and two common sterols. The xanthones are soulattrin (2), caloxanthone C (3), macluraxanthone (4), brasixanthone B (5) and trapezifolixanthone (6) while the sterols are stigmasterol (7) and β-sitosterol (8). The structures of these compounds were determined on the basis of spectroscopic analyses such as 1D and 2D-NMR, HRESIMS, IR and UV. Compounds 1-7 exhibited moderate cytotoxic activities against SNU-1, HeLa, Hep G2, NCI-H23, K562, Raji, LS174T, IMR-32 and SK-MEL-28 cells.
    Matched MeSH terms: Cell Death/drug effects
  12. Fulltext Phosphoinositide-dependent Kinase-1 (PDPK1) regulates serum/glucocorticoid-regulated Kinase 3 (SGK3) for prostate cancer cell survival
    Nalairndran G, Hassan Abdul Razack A, Mai CW, Fei-Lei Chung F, Chan KK, Hii LW, et al.
    J Cell Mol Med, 2020 Oct;24(20):12188-12198.
    PMID: 32926495 DOI: 10.1111/jcmm.15876
    Prostate cancer (PCa) is the most common malignancy and is the second leading cause of cancer among men globally. Using a kinome-wide lentiviral small-hairpin RNA (shRNA) library screen, we identified phosphoinositide-dependent kinase-1 (PDPK1) as a potential mediator of cell survival in PCa cells. We showed that knock-down of endogenous human PDPK1 induced significant tumour-specific cell death in PCa cells (DU145 and PC3) but not in the normal prostate epithelial cells (RWPE-1). Further analyses revealed that PDPK1 mediates cancer cell survival predominantly via activation of serum/glucocorticoid-regulated kinase 3 (SGK3). Knock-down of endogenous PDPK1 in DU145 and PC3 cells significantly reduced SGK3 phosphorylation while ectopic expression of a constitutively active SGK3 completely abrogated the apoptosis induced by PDPK1. In contrast, no such effect was observed in SGK1 and AKT phosphorylation following PDPK1 knock-down. Importantly, PDPK1 inhibitors (GSK2334470 and BX-795) significantly reduced tumour-specific cell growth and synergized docetaxel sensitivity in PCa cells. In summary, our results demonstrated that PDPK1 mediates PCa cells' survival through SGK3 signalling and suggest that inactivation of this PDPK1-SGK3 axis may potentially serve as a novel therapeutic intervention for future treatment of PCa.
    Matched MeSH terms: Cell Death/drug effects
  13. Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N((i)Pr)CH2CH2OH] for R = Ph, Cy and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways
    Jamaludin NS, Goh ZJ, Cheah YK, Ang KP, Sim JH, Khoo CH, et al.
    Eur J Med Chem, 2013 Sep;67:127-41.
    PMID: 23856069 DOI: 10.1016/j.ejmech.2013.06.038
    The synthesis and characterisation of R3PAu[S2CN((i)Pr)CH2CH2OH], for R = Ph (1), Cy (2) and Et (3)4, is reported. Compounds 1-3 are cytotoxic against the doxorubicin-resistant breast cancer cell line, MCF-7R, with 1 exhibiting greater potency and cytotoxicity than either of doxorubicin and cisplatin. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis by 1, and necrosis by 2 and 3, are demonstrated, by both extrinsic and intrinsic pathways. Compound 1 activates the p53 gene, 2 activates only the p73 gene, whereas 3 activates both the p53 and p73 genes. Compounds 1 and 3 activate NF-κB, and each inhibits topoisomerase I.
    Matched MeSH terms: Cell Death/drug effects
  14. Fulltext Persistent infection due to a small-colony variant of Burkholderia pseudomallei leads to PD-1 upregulation on circulating immune cells and mononuclear infiltration in viscera of experimental BALB/c mice
    See JX, Chandramathi S, Abdulla MA, Vadivelu J, Shankar EM
    PLoS Negl Trop Dis, 2017 Aug;11(8):e0005702.
    PMID: 28820897 DOI: 10.1371/journal.pntd.0005702
    BACKGROUND: Melioidosis is a neglected tropical disease endemic across South East Asia and Northern Australia. The etiological agent, Burkholderia pseudomallei (B.pseudomallei), is a Gram-negative, rod-shaped, motile bacterium residing in the soil and muddy water across endemic regions of the tropical world. The bacterium is known to cause persistent infections by remaining latent within host cells for prolonged duration. Reactivation of the recrudescent disease often occurs in elders whose immunity wanes. Moreover, recurrence rates in melioidosis patients can be up to ~13% despite appropriate antibiotic therapy, suggestive of bacterial persistence and inefficacy of antibiotic regimens. The mechanisms behind bacterial persistence in the host remain unclear, and hence understanding host immunity during persistent B. pseudomallei infections may help designing potential immunotherapy.

    METHODOLOGY/PRINCIPAL FINDINGS: A persistent infection was generated using a small-colony variant (SCV) and a wild-type (WT) B. pseudomallei in BALB/c mice via intranasal administration. Infected mice that survived for >60 days were sacrificed. Lungs, livers, spleens, and peripheral blood mononuclear cells were harvested for experimental investigations. Histopathological changes of organs were observed in the infected mice, suggestive of successful establishment of persistent infections. Moreover, natural killer (NK) cell frequency was increased in SCV- and WT-infected mice. We observed programmed death-1 (PD-1) upregulation on B cells of SCV- and WT-infected mice. Interestingly, PD-1 upregulation was only observed on NK cells and monocytes of SCV-infected mice. In contrast, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) downregulation was seen on NK cells of WT-infected mice, and on monocytes of SCV- and WT-infected mice.

    CONCLUSIONS/SIGNIFICANCE: The SCV and the WT of B. pseudomallei distinctly upregulated PD-1 expression on B cells, NK cells, and monocytes to dampen host immunity, which likely facilitates bacterial persistence. PD-1/PD-L1 pathway appears to play an important role in the persistence of B. pseudomallei in the host.

    Matched MeSH terms: Programmed Cell Death 1 Receptor/analysis*
  15. 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
  16. Fulltext Paclitaxel Inhibits Expression of Neuronal Nitric Oxide Synthase and Prevents Mitochondrial Dysfunction in Spinal Ventral Horn in Rats After C7 Spinal Root Avulsion
    Sim SK, Tan YC, Tee JH, Yusoff AA, Abdullah JM
    Turk Neurosurg, 2015;25(4):617-24.
    PMID: 26242340 DOI: 10.5137/1019-5149.JTN.14035-15.1
    This study evaluated the neuroprotective effect of intrathecally infused paclitaxel in the prevention of motoneuron death and mitochondrial dysfunction following brachial plexus avulsion injury.
    Matched MeSH terms: Cell Death/drug effects
  17. Oxidised low density lipoprotein causes human macrophage cell death through oxidant generation and inhibition of key catabolic enzymes
    Katouah H, Chen A, Othman I, Gieseg SP
    Int J Biochem Cell Biol, 2015 Oct;67:34-42.
    PMID: 26255116 DOI: 10.1016/j.biocel.2015.08.001
    Oxidised low density lipoprotein (oxLDL) is thought to be a significant contributor to the death of macrophage cells observed in advanced atherosclerotic plaques. Using human-derived U937 cells we have examined the effect of cytotoxic oxLDL on oxidative stress and cellular catabolism. Within 3h of the addition of oxLDL, there was a rapid, concentration dependent rise in cellular reactive oxygen species followed by the loss of cellular GSH, and the enzyme activity of both glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and aconitase. The loss of these catabolic enzymes was accompanied by the loss of cellular ATP and lower lactate generation. Addition of the macrophage antioxidant 7,8-dihydroneopterin inhibited the ROS generation, glutathione loss and catabolic inactivation. NOX was shown to be activated by oxLDL addition while apocynin inhibited the loss of GSH and cell viability. The data suggests that oxLDL triggers an excess of ROS production through NOX activation, and catabolic failure through thiol oxidation resulting in cell death.
    Matched MeSH terms: Cell Death/drug effects
  18. Oral cancer secretome: identification of cancer-associated proteins
    Chang HY, Hor SY, Lim KP, Zain RB, Cheong SC, Rahman MA, et al.
    Electrophoresis, 2013 Aug;34(15):2199-208.
    PMID: 23712713 DOI: 10.1002/elps.201300126
    This study aims to identify cancer-associated proteins in the secretome of oral cancer cell lines. We have successfully established four primary cell cultures of normal cells with a limited lifespan without human telomerase reverse transcriptase (hTERT) immortalization. The secretome of these primary cell cultures were compared with that of oral cancer cell lines using 2DE. Thirty five protein spots were found to have changed in abundance. Unambiguous identification of these proteins was achieved by MALDI TOF/TOF. In silico analysis predicted that 24 of these proteins were secreted via classical or nonclassical mechanisms. The mRNA expression of six genes was found to correlate with the corresponding protein abundance. Ingenuity Pathway Analysis (IPA) core analysis revealed that the identified proteins were relevant in, and related to, cancer development with likely involvements in tumor growth, metastasis, hyperproliferation, tumorigenesis, neoplasia, hyperplasia, and cell transformation. In conclusion, we have demonstrated that a comparative study of the secretome of cancer versus normal cell lines can be used to identify cancer-associated proteins.
    Matched MeSH terms: Cell Death/physiology
  19. Fulltext Optimization, formulation, and characterization of multiflavonoids-loaded flavanosome by bulk or sequential technique
    Karthivashan G, Masarudin MJ, Kura AU, Abas F, Fakurazi S
    Int J Nanomedicine, 2016;11:3417-34.
    PMID: 27555765 DOI: 10.2147/IJN.S112045
    This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a single phytosome, which can be termed as "flavonosome". Three widely established and therapeutically valuable flavonoids, such as quercetin (Q), kaempferol (K), and apigenin (A), were quantified in the ethyl acetate fraction of Moringa oleifera leaves extract and were commercially obtained and incorporated in a single flavonosome (QKA-phosphatidylcholine) through four different methods of synthesis - bulk (M1) and serialized (M2) co-sonication and bulk (M3) and sequential (M4) co-loading. The study also established an optimal formulation method based on screening the synthesized flavonosomes with respect to their size, charge, polydispersity index, morphology, drug-carrier interaction, antioxidant potential through in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics, and cytotoxicity evaluation against human hepatoma cell line (HepaRG). Furthermore, entrapment and loading efficiency of flavonoids in the optimal flavonosome have been identified. Among the four synthesis methods, sequential loading technique has been optimized as the best method for the synthesis of QKA-phosphatidylcholine flavonosome, which revealed an average diameter of 375.93±33.61 nm, with a zeta potential of -39.07±3.55 mV, and the entrapment efficiency was >98% for all the flavonoids, whereas the drug-loading capacity of Q, K, and A was 31.63%±0.17%, 34.51%±2.07%, and 31.79%±0.01%, respectively. The in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics of the flavonoids indirectly depicts the release kinetic behavior of the flavonoids from the carrier. The QKA-loaded flavonosome had no indication of toxicity toward human hepatoma cell line as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide result, wherein even at the higher concentration of 200 µg/mL, the flavonosomes exert >85% of cell viability. These results suggest that sequential loading technique may be a promising nanodrug delivery system for loading multiflavonoids in a single entity with sustained activity as an antioxidant, hepatoprotective, and hepatosupplement candidate.
    Matched MeSH terms: Cell Death/drug effects
  20. Fulltext Optimization of nanoemulsion containing gemcitabine and evaluation of its cytotoxicity towards human fetal lung fibroblast (MRC5) and human lung carcinoma (A549) cells
    Wahgiman NA, Salim N, Abdul Rahman MB, Ashari SE
    Int J Nanomedicine, 2019;14:7323-7338.
    PMID: 31686809 DOI: 10.2147/IJN.S212635
    Background: Gemcitabine (GEM) is a chemotherapeutic agent, which is known to battle cancer but challenging due to its hydrophilic nature. Nanoemulsion is water-in-oil (W/O) nanoemulsion shows potential as a carrier system in delivering gemcitabine to the cancer cell.

    Methods: The behaviour of GEM in MCT/surfactants/NaCl systems was studied in the ternary system at different ratios of Tween 80 and Span 80. The system with surfactant ratio 3:7 of Tween 80 and Span 80 was chosen for further study on the preparation of nanoemulsion formulation due to the highest isotropic region. Based on the selected ternary phase diagram, a composition of F1 was chosen and used for optimization by using the D-optimal mixture design. The interaction variables between medium chain triglyceride (MCT), surfactant mixture Tween 80: Span 80 (ratio 3:7), 0.9 % sodium chloride solution and gemcitabine were evaluated towards particle size as a response.

    Results: The results showed that NaCl solution and GEM gave more effects on particle size, polydispersity index and zeta potential of 141.57±0.05 nm, 0.168 and -37.10 mV, respectively. The optimized nanoemulsion showed good stability (no phase separation) against centrifugation test and storage at three different temperatures. The in vitro release of gemcitabine at different pH buffer solution was evaluated. The results showed the release of GEM in buffer pH 6.5 (45.19%) was higher than GEM in buffer pH 7.4 (13.62%). The cytotoxicity study showed that the optimized nanoemulsion containing GEM induced cytotoxicity towards A549 cell and at the same time reduced cytotoxicity towards MRC5 when compared to the control (GEM solution).

    Matched MeSH terms: Cell Death/drug effects
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