Displaying publications 41 - 60 of 1027 in total

Abstract:
Sort:
  1. Ahmad U, Ahmed I, Keong YY, Abd Manan N, Othman F
    Biomed Res Int, 2015;2015:127828.
    PMID: 25821783 DOI: 10.1155/2015/127828
    Breast cancer is the malignant tumour that developed from cells of the breast and is the first leading cause of cancer death among women worldwide. Surgery, radiotherapy, and chemotherapy are the available treatments for breast cancer, but these were reported to have side effects. Newcastle disease virus (NDV) known as Avian paramyxovirus type-1 (APMV1) belongs to the genus Avulavirus in a family Paramyxoviridae. NDV is shown to be a promising anticancer agent, killing tumour cells while sparing normal cells unharmed. In this study, the oncolytic and cytotoxic activities of NDV AF2240 strain were evaluated on MDA-MB-231, human mammary carcinoma cell line, using MTT assay, and its inhibitory effects were further studied using proliferation and migration assays. Morphological and apoptotic-inducing effects of NDV on MD-MB-231 cells were observed using phase contrast and fluorescence microscopes. Detection of DNA fragmentation was done following terminal deoxyribonucleotide transferase-mediated Br-dUTP nick end labeling staining (TUNEL) assay, which confirmed that the mode of death was through apoptosis and was quantified by flow cytometry. Furthermore, analysis of cellular DNA content demonstrated that the virus caused an increase in the sub-G1 phase (apoptotic peak) of the cell cycle. It appears that NDV AF2240 strain is a potent anticancer agent that induced apoptosis in time-dependent manner.
    Matched MeSH terms: Cell Line, Tumor
  2. Ahmed Hassan LE, Khadeer Ahamed MB, Abdul Majid AS, Iqbal MA, Al Suede FS, Haque RA, et al.
    PLoS One, 2014;9(6):e90806.
    PMID: 24608571 DOI: 10.1371/journal.pone.0090806
    Tephrosia apollinea is a perennial shrublet widely distributed in Africa and is known to have medicinal properties. The current study describes the bio-assay (cytotoxicity) guided isolation of (-)-pseudosemiglabrin from the aerial parts of T. apollinea. The structural and stereochemical features have been described using spectral and x-ray crystallographic techniques. The cytotoxicity of isolated compound was evaluated against nine cancer cell lines. In addition, human fibroblast was used as a model cell line for normal cells. The results showed that (-)-pseudosemiglabrin exhibited dose-dependent antiproliferative effect on most of the tested cancer cell lines. Selectively, the compound showed significant inhibitory effect on the proliferation of leukemia, prostate and breast cancer cell lines. Further studies revealed that, the compound exhibited proapoptotic phenomenon of cytotoxicity. Interestingly, the compound did not display toxicity against the normal human fibroblast. It can be concluded that (-)-pseudosemiglabrin is worthy for further investigation as a potential chemotherapeutic agent.
    Matched MeSH terms: Cell Line, Tumor
  3. Aisha AF, Ismail Z, Abu-Salah KM, Siddiqui JM, Ghafar G, Abdul Majid AM
    PMID: 23842450 DOI: 10.1186/1472-6882-13-168
    Syzygium campanulatum Korth (Myrtaceae) is an evergreen shrub rich in phenolics, flavonoid antioxidants, and betulinic acid. This study sought to investigate antiangiogenic and anti-colon cancer effects of S.C. standardized methanolic extract.
    Matched MeSH terms: Cell Line, Tumor
  4. Aisha AF, Ismail Z, Abu-Salah KM, Majid AM
    J Pharm Sci, 2012 Feb;101(2):815-25.
    PMID: 22081501 DOI: 10.1002/jps.22806
    α-Mangostin is an oxygenated heterocyclic xanthone with remarkable pharmacological properties, but poor aqueous solubility and low oral bioavailability hinder its therapeutic application. This study sought to improve the compound's solubility and study the mechanism underlying solubility enhancement. Solid dispersions of α-mangostin were prepared in polyvinylpyrrolidone (PVP) by solvent evaporation method and showed substantial enhancement of α-mangostin's solubility from 0.2 ± 0.2 μg/mL to 2743 ± 11 μg/mL. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated interaction between α-mangostin and PVP. Transmission electron microscopy and dynamic light scattering showed self-assembly of round anionic nanomicelles with particle size in the range 99-127 nm. Powder X-ray diffraction indicated conversion of α-mangostin from crystalline into amorphous state, and scanning electron microscopy showed the presence of highly porous powder. Studies using the fluorescent probe pyrene showed that the critical micellar concentration is about 77.4 ± 4 μg/mL. Cellular uptake of nanomicelles was found to be mediated via endocytosis and indicated intracellular delivery of α-mangostin associated with potent cytotoxicity (median inhibitory concentration of 8.9 ± 0.2 μg/mL). Improved solubility, self-assembly of nanomicelles, and intracellular delivery through endocytosis may enhance the pharmacological properties of α-mangostin, particularly antitumor efficacy.
    Matched MeSH terms: Cell Line, Tumor
  5. Aisha AF, Abu-Salah KM, Alrokayan SA, Ismail Z, Abdulmajid AM
    Pak J Pharm Sci, 2012 Jan;25(1):7-14.
    PMID: 22186303
    Parkia speciosa Hassk is a traditional medicinal plant with strong antioxidant and hypoglycemic properties. This study aims to investigate the total phenolic content, antioxidant, cytotoxic and antiangiogenic effect of eight extracts from P. speciosa empty pods. The extracts were found to contain high levels of total phenols and demonstrated strong antioxidant effect in DPPH scavenging test. In rat aortic rings, P. speciosa extracts significantly inhibited the microvessel outgrowth from aortic tissue explants by more than 50%. The antiangiogenic activity was further confirmed by tube formation on matrigel matrix involving human endothelial cells. Cytotoxic effect was evaluated by XTT test on endothelial cells as a model of angiogenesis versus a panel of human cancer and normal cell lines. Basically the extracts did not show acute cytotoxicity. Morphology examination of endothelial cells indicated induction of autophagy characterized by formation of plenty of cytoplasmic vacuoles. The extracts were found to work by decreasing expression of vascular endothelial growth factor in endothelial cells.
    Matched MeSH terms: Cell Line, Tumor
  6. Ajdari Z, Rahman H, Shameli K, Abdullah R, Abd Ghani M, Yeap S, et al.
    Molecules, 2016 Mar 01;21(3):123.
    PMID: 26938520 DOI: 10.3390/molecules21030123
    The current study investigated the anticancer properties of gold nanoparticles (SG-stabilized AuNPs) synthesized using water extracts of the brown seaweed Sargassum glaucescens (SG). SG-stabilized AuNPs were characterized by ultraviolet-visible spectroscopy, transmission and scanning electron microscopy, and energy dispersive X-ray fluorescence spectrometry. The SG-stabilized AuNPs were stable and small at 3.65 ± 1.69 nm in size. The in vitro anticancer effect of SG-stabilized AuNPs was determined on cervical (HeLa), liver (HepG2), breast (MDA-MB-231) and leukemia (CEM-ss) cell lines using fluorescence microscopy, flow cytometry, caspase activity determination, and MTT assays. After 72 h treatment, SG-stabilized AuNPs was shown to be significant (p < 0.05) cytotoxic to the cancer cells in a dose- and time-dependent manner. The IC50 values of SG-stabilized AuNPs on the HeLa, HepG2, CEM-ss, MDA-MB-231 cell lines were 4.75 ± 1.23, 7.14 ± 1.45, 10.32 ± 1.5, and 11.82 ± 0.9 μg/mL, respectively. On the other hand, SG-stabilized AuNPs showed no cytotoxic effect towards the normal human mammary epithelial cells (MCF-10A). SG-stabilized AuNPs significantly (p < 0.05) arrest HeLa cell cycle at G2/M phase and significantly (p < 0.05) activated caspases-3 and -9 activities. The anticancer effect of SG-stabilized AuNPs is via the intrinsic apoptotic pathway. The study showed that SG-stabilized AuNPs is a good candidate to be developed into a chemotherapeutic compound for the treatment of cancers especially cervical cancer.
    Matched MeSH terms: Cell Line, Tumor
  7. Aji G, Huang Y, Ng ML, Wang W, Lan T, Li M, et al.
    Proc Natl Acad Sci U S A, 2020 09 29;117(39):24434-24442.
    PMID: 32917816 DOI: 10.1073/pnas.2007856117
    Sphingolipid dysregulation is often associated with insulin resistance, while the enzymes controlling sphingolipid metabolism are emerging as therapeutic targets for improving insulin sensitivity. We report herein that sphingosine kinase 2 (SphK2), a key enzyme in sphingolipid catabolism, plays a critical role in the regulation of hepatic insulin signaling and glucose homeostasis both in vitro and in vivo. Hepatocyte-specific Sphk2 knockout mice exhibit pronounced insulin resistance and glucose intolerance. Likewise, SphK2-deficient hepatocytes are resistant to insulin-induced activation of the phosphoinositide 3-kinase (PI3K)-Akt-FoxO1 pathway and elevated hepatic glucose production. Mechanistically, SphK2 deficiency leads to the accumulation of sphingosine that, in turn, suppresses hepatic insulin signaling by inhibiting PI3K activation in hepatocytes. Either reexpressing functional SphK2 or pharmacologically inhibiting sphingosine production restores insulin sensitivity in SphK2-deficient hepatocytes. In conclusion, the current study provides both experimental findings and mechanistic data showing that SphK2 and sphingosine in the liver are critical regulators of insulin sensitivity and glucose homeostasis.
    Matched MeSH terms: Cell Line, Tumor
  8. Akhtar MN, Zareen S, Yeap SK, Ho WY, Lo KM, Hasan A, et al.
    Molecules, 2013 Aug 20;18(8):10042-55.
    PMID: 23966087 DOI: 10.3390/molecules180810042
    Naturally occurring anthraquinones, damnacanthal (1) and nordamnacanthal (2) were synthesized with modified reaction steps and investigated for their cytotoxicity against the MCF-7 and K-562 cancer cell lines, respectively. Intermediate analogues 2-bromomethyl-1,3-dimethoxyanthraquinone (5, IC50 = 5.70 ± 0.21 and 8.50 ± 1.18 mg/mL), 2-hydroxymethyl-1,3-dimethoxyanthraquinone (6, IC50 = 12.10 ± 0.14 and 14.00 ± 2.13), 2-formyl-1,3-dimethoxyantharquinone (7, IC50 = 13.10 ± 1.02 and 14.80 ± 0.74), 1,3-dimethoxy-2-methylanthraquinone (4, IC50 = 9.40 ± 3.51 and 28.40 ± 2.33), and 1,3-dihydroxy-2-methylanthraquinone (3, IC50 = 25.60 ± 0.42 and 28.40 ± 0.79) also exhibited moderate cytotoxicity against MCF-7 and K-562 cancer cell lines, respectively. Other structurally related compounds like 1,3-dihydroxyanthraquinone (13a, IC50 = 19.70 ± 0.35 and 14.50 ± 1.28), 1,3-dimethoxyanthraquinone (13b, IC50 = 6.50 ± 0.66 and 5.90 ± 0.95) were also showed good cytotoxicity. The target compound damnacanthal (1) was found to be the most cytotoxic against the MCF-7 and K-562 cancer cell lines, with IC50 values of 3.80 ± 0.57 and 5.50 ± 1.26, respectively. The structures of all compounds were elucidated with the help of detailed spectroscopic techniques.
    Matched MeSH terms: Cell Line, Tumor
  9. Akinsola RO, Lee CW, Sim EUH, Narayanan K
    Anal Biochem, 2021 03 01;616:114088.
    PMID: 33358938 DOI: 10.1016/j.ab.2020.114088
    Endosomal escape is considered a crucial barrier that needs to be overcome by integrin-mediated E. coli for gene delivery into mammalian cells. Bafilomycin, a potent inhibitor of the H+ proton pump commonly employed to lower endosomal pH, was evaluated as part of the E. coli protocol during delivery. We found an increase in green fluorescent protein expression up 6.9, 3.2, 5.0, 2.8, and 4.5 fold in HeLa, HEK-293, A549, HT1080, and MCF-7 respectively, compared to untreated cells. Our result showed for the first time that Inhibition of lysosomal V-ATPase enhances E. coli efficiency.
    Matched MeSH terms: Cell Line, Tumor
  10. Al-Afifi NA, Alabsi AM, Shaghayegh G, Ramanathan A, Ali R, Alkoshab M, et al.
    Arch Oral Biol, 2019 Aug;104:77-89.
    PMID: 31176147 DOI: 10.1016/j.archoralbio.2019.05.030
    OBJECTIVE: To study the potential for apoptosis induction of Dracaena cinnabari Balf. f methanolic extract (DCBME) on tongue squamous cell carcinoma cell line, H103. We evaluated the chemopreventive activity of DCBME against 4-nitroquinolone-1-oxide (4NQO)-induced tongue carcinogenesis in rat.

    DESIGN: Phase contrast microscope, acridine orange/propidium iodide (AO/PI) analysis of cells under fluorescence microscope, annexin-V flow-cytometry, DNA fragmentation, mitochondrial membrane potential, and caspase 3/7, 8 and 9 assays were performed. In vivo study, the rats were given 4NQO in their drinking water. The tongue was subjected to histopathological study to evaluate the incidence of squamous cell carcinoma (SCC).

    RESULTS: DCBME showed cytotoxic effect on H103 cells in a dose- and time-dependent manner. Furthermore, DCBME showed low cytotoxic effect on a normal cell line. In H103 cells, it caused cell morphology changes, S and G2/M-phase cell cycle arrest, significant reduction of cell migration and induced apoptosis through the intrinsic (mitochondrial) pathway. The incidence of SCC was 85.7% in the induced cancer and vehicle groups while in rats treated with DCBME at 100, 500 and 1000 mg/kg was 57.1%, 28.6% and 14.3%, respectively.

    CONCLUSIONS: (DCBME)-apoptosis induction reported in this work can be exploited as a potential antitumor agent with applications in medicinal treatments of tongue SCC.

    Matched MeSH terms: Cell Line, Tumor
  11. Al-Amin M, Eltayeb NM, Khairuddean M, Salhimi SM
    Nat Prod Res, 2021 Sep;35(18):3166-3170.
    PMID: 31726856 DOI: 10.1080/14786419.2019.1690489
    Rhizomes of Curcuma caesia are traditionally used to treat cancer in India. The aim is to isolate chemical constituents from C. caesia rhizomes through bioassay-guided fractionation. The extract, hexanes and chloroform fractions showed effect on MCF-7 and MDA-MB-231cells in cell viability assay. The chromatographic separation afforded germacrone (1), zerumbone (2), furanodienone (3), curzerenone (4), curcumenol (5), zederone (6), curcumenone (7), dehydrocurdione (8) from hexanes fraction and curcuminol G (9), curcuzederone (10), (1S, 10S), (4S,5S)-germacrone-1 (10), 4-diepoxide (11), wenyujinin B (12), alismoxide (13), aerugidiol (14), zedoarolide B (15), zedoalactone B (16), zedoarondiol (17), isozedoarondiol (18) from chloroform fraction. This is first report of compounds 2, 9-13, 15-18 from C. caesia. The study demonstrated compounds 1-4 and 10 are the bioactive compounds. The effect of curcuzederone (10) on MDA-MB-231 cell migration showed significant inhibition in scratch and Transwell migration assays. The results revealed that curcuzederone could be a promising drug to treat cancer.
    Matched MeSH terms: Cell Line, Tumor
  12. Al-Amin M, Eltayeb NM, Hossain CF, Khairuddean M, Fazalul Rahiman SS, Salhimi SM
    Planta Med, 2020 Apr;86(6):387-394.
    PMID: 32168546 DOI: 10.1055/a-1129-7026
    Zingiber montanum rhizomes are traditionally used for the treatment of numerous human ailments. The present study was carried out to investigate the inhibitory activity of the crude extract, chromatographic fractions, and purified compounds from Z. montanum rhizomes on the migration of MDA-MB-231 cells. The effect of the extract on cell migration was investigated by a scratch assay, which showed significant inhibition in a concentration-dependent manner. Vacuum liquid chromatography on silica gel afforded four fractions (Frs. 1 - 4), which were tested on cell migration in the scratch assay. Frs. 1 and 2 showed the most significant inhibition of MDA-MB-231 cell migration. The effect of the most potent fraction (Fr. 2) was further confirmed in a transwell migration assay. The study of Frs. 1 and 2 by gelatin zymography showed significant inhibition of MMP-9 enzyme activity. Chromatographic separation of Frs. 1 and 2 afforded buddledone A (1: ), zerumbone (2: ), (2E,9E)-6-methoxy-2,9-humuradien-8-one (3: ), zerumbone epoxide (4: ), stigmasterol (5: ), and daucosterol (6: ). In a cell viability assay, compounds 1:  - 4: inhibited the viability of MDA-MB-231 cells in a concentration-dependent manner. The study of buddledone A (1: ) and zerumbone epoxide (4: ) on cell migration revealed that 4: significantly inhibited the migration of MDA-MB-231 cells in both scratch and transwell migration assays. The results of the present study may lead to further molecular studies behind the inhibitory activity of zerumbone epoxide (4: ) on cell migration and support the traditional use of Z. montanum rhizomes for the treatment of cancer.
    Matched MeSH terms: Cell Line, Tumor
  13. Al-Anazi M, Al-Najjar BO, Khairuddean M
    Molecules, 2018 Dec 05;23(12).
    PMID: 30563058 DOI: 10.3390/molecules23123203
    Human Epidermal Growth Factor Receptor-1 (EGFR), a transmembrane tyrosine kinase receptor (RTK), has been associated with several types of cancer, including breast, lung, ovarian, and anal cancers. Thus, the receptor was targeted by a variety of therapeutic approaches for cancer treatments. A series of chalcone derivatives are among the most highly potent and selective inhibitors of EGFR described to date. A series of chalcone derivatives were proposed in this study to investigate the intermolecular interactions in the active site utilizing molecular docking and molecular dynamics simulations. After a careful analysis of docking results, compounds 1a and 1d were chosen for molecular dynamics simulation study. Extensive hydrogen bond analysis throughout 7 ns molecular dynamics simulation revealed the ability of compounds 1a and 1d to retain the essential interactions needed for the inhibition, especially MET 93. Finally, MM-GBSA calculations highlight on the capability of the ligands to bind strongly within the active site with binding energies of -44.04 and -56.6 kcal/mol for compounds 1a and 1d, respectively. Compound 1d showed to have a close binding energy with TAK-285 (-66.17 kcal/mol), which indicates a high chance for compound 1d to exhibit inhibitory activity, thus recommending to synthesis it to test its biological activity. It is anticipated that the findings reported here may provide very useful information for designing effective drugs for the treatment of EGFR-related cancer disease.
    Matched MeSH terms: Cell Line, Tumor
  14. Al-Ani LA, Yehye WA, Kadir FA, Hashim NM, AlSaadi MA, Julkapli NM, et al.
    PLoS One, 2019;14(5):e0216725.
    PMID: 31086406 DOI: 10.1371/journal.pone.0216725
    Nanotechnology-based antioxidants and therapeutic agents are believed to be the next generation tools to face the ever-increasing cancer mortality rates. Graphene stands as a preferred nano-therapeutic template, due to the advanced properties and cellular interaction mechanisms. Nevertheless, majority of graphene-based composites suffer from hindered development as efficient cancer therapeutics. Recent nano-toxicology reviews and recommendations emphasize on the preliminary synthetic stages as a crucial element in driving successful applications results. In this study, we present an integrated, green, one-pot hybridization of target-suited raw materials into curcumin-capped gold nanoparticle-conjugated reduced graphene oxide (CAG) nanocomposite, as a prominent anti-oxidant and anti-cancer agent. Distinct from previous studies, the beneficial attributes of curcumin are employed to their fullest extent, such that they perform dual roles of being a natural reducing agent and possessing antioxidant anti-cancer functional moiety. The proposed novel green synthesis approach secured an enhanced structure with dispersed homogenous AuNPs (15.62 ± 4.04 nm) anchored on reduced graphene oxide (rGO) sheets, as evidenced by transmission electron microscopy, surpassing other traditional chemical reductants. On the other hand, safe, non-toxic CAG elevates biological activity and supports biocompatibility. Free radical DPPH inhibition assay revealed CAG antioxidant potential with IC50 (324.1 ± 1.8%) value reduced by half compared to that of traditional citrate-rGO-AuNP nanocomposite (612.1 ± 10.1%), which confirms the amplified multi-potent antioxidant activity. Human colon cancer cell lines (HT-29 and SW-948) showed concentration- and time-dependent cytotoxicity for CAG, as determined by optical microscopy images and WST-8 assay, with relatively low IC50 values (~100 μg/ml), while preserving biocompatibility towards normal human colon (CCD-841) and liver cells (WRL-68), with high selectivity indices (≥ 2.0) at all tested time points. Collectively, our results demonstrate effective green synthesis of CAG nanocomposite, free of additional stabilizing agents, and its bioactivity as an antioxidant and selective anti-colon cancer agent.
    Matched MeSH terms: Cell Line, Tumor
  15. Al-Fahdawi MQ, Al-Doghachi FAJ, Abdullah QK, Hammad RT, Rasedee A, Ibrahim WN, et al.
    Biomed Pharmacother, 2021 Jun;138:111483.
    PMID: 33744756 DOI: 10.1016/j.biopha.2021.111483
    The aim of this study was to prepare, characterize, and determine the in vitro anticancer effects of platinum-doped magnesia (Pt/MgO) nanoparticles. The chemical compositions, functional groups, and size of nanoparticles were determined using X-ray diffraction, Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. Pt/MgO nanoparticles were cuboid and in the nanosize range of 30-50 nm. The cytotoxicity of Pt/MgO nanoparticles was determined via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on the human lung and colonic cancer cells (A549 and HT29 respectively) and normal human lung and colonic fibroblasts cells (MRC-5 and CCD-18Co repectively). The Pt/MgO nanoparticles were relatively innocuous to normal cells. Pt/MgO nanoparticles downregulated Bcl-2 and upregulated Bax and p53 tumor suppressor proteins in the cancer cells. Pt/MgO nanoparticles also induced production of reactive oxygen species, decreased cellular glutathione level, and increased lipid peroxidation. Thus, the anticancer effects of Pt/MgO nanoparticles were attributed to the induction of oxidative stress and apoptosis. The study showed the potential of Pt/MgO nanoparticles as an anti-cancer compound.
    Matched MeSH terms: Cell Line, Tumor
  16. Al-Henhena N, Khalifa SA, Ying RP, Ismail S, Hamadi R, Shawter AN, et al.
    BMC Complement Altern Med, 2015;15(1):419.
    PMID: 26608653 DOI: 10.1186/s12906-015-0926-7
    With cancer being one of the major causes of death around the world, studies are ongoing to find new chemotherapeutic leads. There are common mechanisms for colorectal cancer (CRC) formation. Several are connected with oxidative stress-induced cell apoptosis and others are related to imbalanced homeostasis or intake of drugs/toxins. Plants that have been used for decades in folk and traditional medicine have been accepted as one of the commonest sources of discovered natural agents of cancer chemotherapy and chemoprevention. The aim was to study the antioxidant and chemopreventive effects of Strobilanthes crispus on colorectal cancer formation.
    Matched MeSH terms: Cell Line, Tumor/drug effects
  17. Al-Henhena N, Ying RP, Ismail S, Najm W, Najm W, Khalifa SA, et al.
    PLoS One, 2014;9(11):e111118.
    PMID: 25390042 DOI: 10.1371/journal.pone.0111118
    Andrographis paniculata is a grass-shaped medicinal herb, traditionally used in Southeast Asia. The aim of this study was to evaluate the chemoprotective effects of A. paniculata on colorectal cancer. A. paniculata ethanol extract was tested on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in vivo and in vitro. A. paniculata treated groups showed a significant reduction in the number of ACF of the treated rats. Microscopically, ACF showed remarkably elongated and stratified cells, and depletion of the submucosal glands of AOM group compared to the treated groups. Histologically, staining showed slightly elevated masses above the surrounding mucosa with oval or slit-like orifices. Immunohistochemically, expression of proliferating cell nuclear antigen (PCNA) and β-catenin protein were down-regulated in the A. paniculata treated groups compared to the AOM group. When colon tissue was homogenized, malondialdehyde (MDA) and nitric oxide (NO) levels were significantly decreased, whereas superoxide dismutase (SOD) activity was increased in the treated groups compared to the AOM group. A. paniculata ethanol extract showed antioxidant and free radical scavenging activity, as elucidated by the measure of oxidative stress markers. Further, the active fractions were assessed against cell lines of CCD841 and HT29 colon cancer cells.
    Matched MeSH terms: Cell Line, Tumor
  18. Al-Jamal HA, Jusoh SA, Yong AC, Asan JM, Hassan R, Johan MF
    Asian Pac J Cancer Prev, 2014;15(11):4555-61.
    PMID: 24969884
    BACKGROUND: Silencing due to methylation of suppressor of cytokine signaling-3 (SOCS-3), a negative regulator gene for the JAK/STAT signaling pathway has been reported to play important roles in leukemogenesis. Imatinib mesylate is a tyrosine kinase inhibitor that specifically targets the BCR-ABL protein and induces hematological remission in patients with chronic myeloid leukemia (CML). Unfortunately, the majority of CML patients treated with imatinib develop resistance under prolonged therapy. We here investigated the methylation profile of SOCS-3 gene and its downstream effects in a BCR-ABL positive CML cells resistant to imatinib.

    MATERIALS AND METHODS: BCR-ABL positive CML cells resistant to imatinib (K562-R) were developed by overexposure of K562 cell lines to the drug. Cytotoxicity was determined by MTS assays and IC50 values calculated. Apoptosis assays were performed using annexin V-FITC binding assays and analyzed by flow cytometry. Methylation profiles were investigated using methylation specific PCR and sequencing analysis of SOCS-1 and SOCS-3 genes. Gene expression was assessed by quantitative real-time PCR, and protein expression and phosphorylation of STAT1, 2 and 3 were examined by Western blotting.

    RESULTS: The IC50 for imatinib on K562 was 362 nM compared to 3,952 nM for K562-R (p=0.001). Percentage of apoptotic cells in K562 increased upto 50% by increasing the concentration of imatinib, in contrast to only 20% in K562-R (p<0.001). A change from non-methylation of the SOCS-3 gene in K562 to complete methylation in K562-R was observed. Gene expression revealed down- regulation of both SOCS-1 and SOCS-3 genes in resistant cells. STAT3 was phosphorylated in K562-R but not K562.

    CONCLUSIONS: Development of cells resistant to imatinib is feasible by overexposure of the drug to the cells. Activation of STAT3 protein leads to uncontrolled cell proliferation in imatinib resistant BCR-ABL due to DNA methylation of the SOCS-3 gene. Thus SOCS-3 provides a suitable candidate for mechanisms underlying the development of imatinib resistant in CML patients.

    Matched MeSH terms: Cell Line, Tumor
  19. Al-Majedy YK, Al-Amiery AA, Kadhum AA, Mohamad AB
    PLoS One, 2016;11(5):e0156625.
    PMID: 27243231 DOI: 10.1371/journal.pone.0156625
    The synthesis of derivatives of 4-Methylumbelliferone (4-MUs), which are structurally interesting antioxidants, was performed in this study. The modification of 4-Methylumbelliferone (4-MU) by different reaction steps was performed to yield the target compounds, the 4-MUs. The 4-MUs were characterized by different spectroscopic techniques (Fourier transform infrared; FT-IR and Nuclear magnetic resonance; NMR) and micro-elemental analysis (CHNS). The in vitro antioxidant activity of the 4-MUs was evaluated in terms of their free radical scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH), Nitric oxide radical scavenging activity assay, chelating activity and their (FRAP) ferric-reducing antioxidant power, which were compared with a standard antioxidant. Our results reveal that the 4-MUs exhibit excellent radical scavenging activities. The antioxidant mechanisms of the 4-MUs were also studied. Density Function Theory (DFT)-based quantum chemical studies were performed with the basis set at 3-21G. Molecular models of the synthesized compounds were studied to understand the antioxidant activity. The electron levels, namely HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital), for these synthesized antioxidants were also studied.
    Matched MeSH terms: Cell Line, Tumor
  20. Al-Maleki AR, Mariappan V, Vellasamy KM, Shankar EM, Tay ST, Vadivelu J
    J Proteomics, 2014 Jun 25;106:205-20.
    PMID: 24742602 DOI: 10.1016/j.jprot.2014.04.005
    Colony morphology variation is a characteristic of Burkholderia pseudomallei primary clinical isolates, associated with variations in expression of virulence factors. Here, we performed comparative investigations on adhesion, invasion, plaque-forming abilities and protein profiles of B. pseudomallei wild-type (WT) and a small colony variant (SCV). The percentage of SCV adherence to A549 cells was significantly higher (2.73%) than WT (1.91%). In contrast, WT was significantly more efficient (0.63%) than SCV (0.31%) in invasiveness and in inducing cellular damage. Using 2-DE and MALDI TOF/TOF, 263 and 258 protein spots were detected in WT and SCV, respectively. Comparatively, 49 proteins were differentially expressed in SCV when compared with WT. Of these, 31 proteins were up-regulated, namely, nucleoside diphosphate kinase (Ndk), phosphoglycerate kinase (Pgk), thioredoxin (TrxA), putative ferritin DPS-family DNA-binding protein (DPS) and oxidoreductase (AhpC) that are known to be involved in adhesion, intracellular survival and persistence. However, among the 18 down-regulated proteins, enolase (Eno), elongation factor (EF-Tu) and universal stress-related proteins were associated with invasion and virulence. Differences observed in these protein profiles provide ample clues to their association with the morphotypic and phenotypic characteristics of colony variants, providing additional insights into the potential association of B. pseudomallei colony morphotypes with disease pathogenesis.
    Matched MeSH terms: Cell Line, Tumor
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links