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  1. Design, synthesis, and biological evaluation of 1,8-naphthyridine glucosamine conjugates as antimicrobial agents
    Mohammed AAM, Suaifan GARY, Shehadeh MB, Okechukwu PN
    Drug Dev Res, 2019 02;80(1):179-186.
    PMID: 30570767 DOI: 10.1002/ddr.21508
    In the quest for discovering potent antimicrobial agents with lower toxicity, we envisioned the design and synthesis of nalidixic acid-D-(+)-glucosamine conjugates. The novel compounds were synthesized and evaluated for their in vitro antimicrobial activity against Gram positive bacteria, Gram negative bacteria and fungi. Cytotoxicity using MTT assay over L6 skeletal myoblast cell line, ATCC CRL-1458 was carried out. In vitro antimicrobial assay revealed that 1-ethyl-7-methyl-4-oxo-N-(1,3,4,6-tetra-O-acetyl-2-deoxy-D-glucopyranose-2-yl)-[1,8]-naphthyridine-3-carboxamide (5) and 1-ethyl-7-methyl-4-oxo-N-(2-deoxy-D-glucopyranose-2-yl)-[1,8]-naphthyridine-3-carboxamide(6) possess growth inhibitory activity against resistant Escherichia coli NCTC, 11954 (MIC 0.1589 mM) and Methicillin resistant Staphylococcus aureus ATCC, 33591 (MIC 0.1589 mM). Compound (5) was more active against Listeria monocytogenes ATCC 19115 (MIC 0.1113 mM) in comparison with the reference nalidixic acid (MIC 1.0765 mM). Interestingly, compound (6) had potential antifungal activity against Candida albicans ATCC 10231 (MIC <0.0099 mM). Remarkably, the tested compounds had low cytotoxic effect. This study indicated that glucosamine moiety inclusion into the chemical structure of the marketed nalidixic acid enhances antimicrobial activity and safety.
    Matched MeSH terms: Cell Line
  2. Fulltext Structure-Based Drug Design Studies Toward the Discovery of Novel Chalcone Derivatives as Potential Epidermal Growth Factor Receptor (EGFR) Inhibitors
    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
  3. Fulltext Zerumbone Induces Apoptosis in Breast Cancer Cells by Targeting αvβ3 Integrin upon Co-Administration with TP5-iRGD Peptide
    E M Eid E, S Alanazi A, Koosha S, A Alrasheedy A, Azam F, M Taban I, et al.
    Molecules, 2019 Jul 13;24(14).
    PMID: 31337024 DOI: 10.3390/molecules24142554
    Cell-penetrating peptides (CPPs) are highly promising tools to deliver therapeutic molecules into tumours. αVβ3 integrins are cell-matrix adhesion receptors, and are considered as an attractive target for anticancer therapies owing to their roles in the process of metastasis and angiogenesis. Therefore, this study aims to assess the effect of co-administration of zerumbone (ZER) and ZERencapsulated in hydroxypropyl-β-cyclodextrin with TP5-iRGD peptide towards cell cytotoxicity, apoptosis induction, and proliferation of normal and cancerous breast cells utilizing in vitro assays, as well as to study the molecular docking of ZER in complex with TP5-iRGD peptide. Cell viability assay findings indicated that ZER and ZERencapsulated in hydroxypropyl-β-cyclodextrin (ZER-HPβCD) inhibited the growth of estrogen receptor positivebreast cancer cells (ER+ MCF-7) at 72 h treatment with an inhibitory concentration (IC)50 of 7.51 ± 0.2 and 5.08 ± 0.2 µg/mL, respectively, and inhibited the growth of triple negative breast cancer cells (MDA-MB-231) with an IC50 of 14.96 ± 1.52 µg/mL and 12.18 ± 0.7 µg/mL, respectively. On the other hand, TP5-iRGD peptide showed no significant cytotoxicity on both cancer and normal cells. Interestingly, co-administration of TP5-iRGD peptide in MCF-7 cells reduced the IC50 of ZER from 7.51 ± 0.2 µg/mL to 3.13 ± 0.7 µg/mL and reduced the IC50 of ZER-HPβCD from 5.08 ± 0.2 µg/mL to 0.49 ± 0.004 µg/mL, indicating that the co-administration enhances the potency and increases the efficacy of ZER and ZER-HPβCD compounds. Acridine orange (AO)/propidium iodide (PI) staining under fluorescence microscopy showed evidence of early apoptosis after 72 h from the co-administration of ZER or ZER-HPβCD with TP5-iRGD peptide in MCF-7 breast cancer cells. The findings of the computational modelling experiment provide novel insights into the ZER interaction with integrin αvβ3 in the presence of TP5-iRGD, and this could explain why ZER has better antitumor activities when co-administered with TP5-iRGD peptide.
    Matched MeSH terms: Cell Line, Tumor
  4. Investigations into the therapeutic effects of aerial and stem parts of Buxus papillosa C.K. Schneid.: In vitro chemical, biological and toxicological perspectives
    Saleem H, Htar TT, Naidu R, Ahmad I, Zengin G, Ahmad M, et al.
    J Pharm Biomed Anal, 2019 Mar 20;166:128-138.
    PMID: 30640043 DOI: 10.1016/j.jpba.2019.01.007
    In this study, different solvent extracts (methanol, dichloromethane and n-hexane) from aerial and stem parts of Buxus papillosa C.K. Schneid (Buxaceae) were investigated for a panoply of bioassays. Biological profiles were established by determining antioxidant and enzyme inhibition profiles. Toxicity was tested using MTT cell viability assay on five different human cancer cell lines i.e, MCF-7, MDA-MB-231, CaSki, DU-145 and SW-480. For chemical fingerprinting, total bioactive contents and UHPLC-MS secondary metabolites profile were determined. Generally, both aerial and stem methanol extracts had highest total bioactive contents, radical scavenging and reducing power potential. DCM and n-hexane extracts were found to be most active for total antioxidant and metal chelating activity. The UHPLC-MS analysis of methanol extracts revealed the presence of several phenolic, flavonoid, alkaloid, saponin and depsipeptide derivatives. All the extracts were significantly active against butyrylcholinesterase, whereas moderate inhibition was observed for acetylcholinesterase, α-glucosidase and urease. Similarly, a considerable level of cytotoxicity was observed against all the tested cell lines with IC50 values ranging from 26 to 225.9 μg/mL. Aerial methanol and stem n-hexane extracts were found to be most cytotoxic. Principal component analysis was also performed to find any possible correlation between biological activities and total bioactive contents. On the basis of our findings, B. papillosa may be considered as promising source of bioactive molecules.
    Matched MeSH terms: Cell Line, Tumor
  5. Differential cytotoxic activity of Quercetin on colonic cancer cells depends on ROS generation through COX-2 expression
    Raja SB, Rajendiran V, Kasinathan NK, P A, Venkatabalasubramanian S, Murali MR, et al.
    Food Chem Toxicol, 2017 Aug;106(Pt A):92-106.
    PMID: 28479391 DOI: 10.1016/j.fct.2017.05.006
    Quercetin is a bioactive compound with anti-inflammatory, antioxidant and anticancer properties. This study exemplifies the differential cytotoxic activity of Quercetin on two human colonic cancer cell lines, HT29 and HCT15. IC50 of Quercetin for HT29 and HCT15 cells were 42.5 μM and 77.4 μM, respectively. Activation of caspase-3, increased level of cytosolic cytochrome c, decreased levels of pAkt, pGSK-3β and cyclin D1 in 40 μM Quercetin treated HT29 cells alone. Though, nuclear translocation of NFkB was increased in 40 μM Quercetin treated HT29 and HCT15 cells, over expression of COX-2 was observed in 40 μM Quercetin treated HT29 cells, whereas, Quercetin treated HCT15 cells did not expressed COX-2. Increased generation of reactive oxygen species (ROS) was observed only in Quercetin treated HT29 cells, which is due to over expression of COX-2, as COX-2 silencing inhibited Quercetin induced apoptosis and ROS generation. Insilico analysis provided evidence that Quercetin could partially inhibit COX-2 enzyme by binding to subunit A which has peroxidase activity and serves as source of ROS. However, Quercetin showed minimal effect on normal intestinal epithelial cells i,e IEC-6. To conclude, differential sensitivity of two cancer cells, HT29 and HCT15, to Quercetin depends on COX-2 dependent ROS generation that induces apoptosis and inhibits cell survival.
    Matched MeSH terms: Cell Line, Tumor
  6. Cytotoxic xanthones isolated from Calophyllum depressinervosum and Calophyllum buxifolium with antioxidant and cytotoxic activities
    Zamakshshari NH, Ee GCL, Ismail IS, Ibrahim Z, Mah SH
    Food Chem Toxicol, 2019 Nov;133:110800.
    PMID: 31479710 DOI: 10.1016/j.fct.2019.110800
    The stem bark of Calophyllum depressinervosum and Calophyllum buxifolium were extracted and examined for their antioxidant activities, together with cytotoxicity towards human cancer cells. The methanol extract of C. depressinervosum exhibited good DPPH and NO scavenging effects. The strongest BCB inhibition and FIC effects were shown by dichloromethane and ethyl acetate extracts of both species. Overall, DPPH, FRAP and FIC assays showed strong correlation with TPC. For cytotoxicity, hexane extract of C. depressinervosum possessed the strongest anti-proliferative activities towards SNU-1 cells while the hexane extract of C. buxifolium showed the strongest activity towards LS-174T and K562 cells with the IC50 values ranging from 7 to 17 μg/mL. The purification of plant extracts afforded eight xanthones, ananixanthone (1), caloxanthone B (2), caloxanthone I (3), caloxanthone J (4) xanthochymone B (5), thwaitesixanthone (6), 1,3,5,6-tetrahydroxyxanthone (7) and dombakinaxanthone (8). All the xanthones, except 1 were reported for the first time from both Calophyllum species. The xanthones were examined for their cytotoxic effect against K562 leukemic cells. Compounds 1 and 2 showed strong cytotoxicity with the IC50 values of 2.96 and 1.23 μg/mL, respectively. The molecular binding interaction of 2 was further investigated by performing molecular docking study with promising protein receptor Src kinase.
    Matched MeSH terms: Cell Line, Tumor
  7. Determination toxic effects of Hystrix Brachyura Bezoar extracts using cancer cell lines and embryo zebrafish (Danio rerio) models and identification of active principles through GC-MS analysis
    Firus Khan AY, Ahmed QU, Nippun TS, Hilles A, Jalal TK, Teh LK, et al.
    J Ethnopharmacol, 2020 Nov 15;262:113138.
    PMID: 32726681 DOI: 10.1016/j.jep.2020.113138
    ETHNOPHARMACOLOGICAL RELEVANCE: Porcupine bezoar (PB) is used as folk medicine for various medical conditions including cancer treatment in Malaysia. However, its toxicity profile has never been thoroughly ascertained to confirm its safe nature as an efficacious traditional medicine in the treatment of cancer as well as other ailments.

    AIM OF THE STUDY: This study was aimed to reveal three different PBs' aqueous extracts(viz. PB-A, PB-B, PB-C) chemical constituent's profile using GC-MS analysis, anticancer property on A375, HeLa and MCF7 cancer cells, toxicity profile on zebrafish embryo morphology, EC50, LC50 and teratogenicity index.

    MATERIALS AND METHODS: PBs' extracts characterization was performed through GC-MS analysis, in vitro anticancer effect was carried out on A375, HeLa and MCF7 cancer cell lines and finally and toxicity properties on three different PBs aqueous extracts (viz. PB-A, PB-B, PB-C) were determined using zebrafish embryo model.

    RESULTS: The GC-MS analysis revealed 10 similar compounds in all PBs' extracts. Dilauryl thiodipropionate was found to be a major compound in all PBs' extracts followed by tetradecanoic acid. An in vitro anticancer study revealed PB extracts exerted median inhibition concentration (IC50) <50 μg/mL, on cancer cells viz. A375, HeLa and MCF7 with no significant toxicity on normal cells viz. NHDF cells. In vivo toxicity of PBs extracts found affecting tail detachment, hatching, craniofacial, brain morphology, soft tissues, edema, spinal, somites, notochord and cardiovascular system (brachycardia, disruption of blood circulation) deformities. The LC50 and EC50 demonstrated PB extracts effect as dose and time dependent with median concentration <150.0 μg/mL. Additionally, teratogenicity index (TI) viz. >1.0 revealed teratogenic property for PB extracts.

    CONCLUSIONS: The findings revealed that all three PBs aqueous extracts possessed anticancer activity and exhibited significant toxicological effects on zebrafish embryos with high teratogenicity index. Hence, its use as an anticancer agent requires further investigation and medical attentions to determine its safe dose.

    Matched MeSH terms: Cell Line, Tumor
  8. Fulltext Knockdown of Tousled‑like kinase 1 inhibits survival of glioblastoma multiforme cells
    Ibrahim K, Abdul Murad NA, Harun R, Jamal R
    Int J Mol Med, 2020 Aug;46(2):685-699.
    PMID: 32468002 DOI: 10.3892/ijmm.2020.4619
    Glioblastoma multiforme (GBM) is an aggressive type of brain tumour that commonly exhibits resistance to treatment. The tumour is highly heterogenous and complex kinomic alterations have been reported leading to dysregulation of signalling pathways. The present study aimed to investigate the novel kinome pathways and to identify potential therapeutic targets in GBM. Meta‑analysis using Oncomine identified 113 upregulated kinases in GBM. RNAi screening was performed on identified kinases using ON‑TARGETplus siRNA library on LN18 and U87MG. Tousled‑like kinase 1 (TLK1), which is a serine/threonine kinase was identified as a potential hit. In vitro functional validation was performed as the role of TLK1 in GBM is unknown. TLK1 knockdown in GBM cells significantly decreased cell viability, clonogenicity, proliferation and induced apoptosis. TLK1 knockdown also chemosensitised the GBM cells to the sublethal dose of temozolomide. The downstream pathways of TLK1 were examined using microarray analysis, which identified the involvement of DNA replication, cell cycle and focal adhesion signalling pathways. In vivo validation of the subcutaneous xenografts of stably transfected sh‑TLK1 U87MG cells demonstrated significantly decreased tumour growth in female BALB/c nude mice. Together, these results suggested that TLK1 may serve a role in GBM survival and may serve as a potential target for glioma.
    Matched MeSH terms: Cell Line, Tumor
  9. Fulltext In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR Inhibitors
    Zulkipli NN, Zakaria R, Long I, Abdullah SF, Muhammad EF, Wahab HA, et al.
    Molecules, 2020 Sep 02;25(17).
    PMID: 32887218 DOI: 10.3390/molecules25173991
    Natural products remain a popular alternative treatment for many ailments in various countries. This study aimed to screen for potential mammalian target of rapamycin (mTOR) inhibitors from Malaysian natural substance, using the Natural Product Discovery database, and to determine the IC50 of the selected mTOR inhibitors against UMB1949 cell line. The crystallographic structure of the molecular target (mTOR) was obtained from Protein Data Bank, with Protein Data Bank (PDB) ID: 4DRI. Everolimus, an mTOR inhibitor, was used as a standard compound for the comparative analysis. Computational docking approach was performed, using AutoDock Vina (screening) and AutoDock 4.2.6 (analysis). Based on our analysis, asiaticoside and its derivative, asiatic acid, both from Centella asiatica, revealed optimum-binding affinities with mTOR that were comparable to our standard compound. The effect of asiaticoside and asiatic acid on mTOR inhibition was validated with UMB1949 cell line, and their IC50 values were 300 and 60 µM, respectively, compared to everolimus (29.5 µM). Interestingly, this is the first study of asiaticoside and asiatic acid against tuberous sclerosis complex (TSC) disease model by targeting mTOR. These results, coupled with our in silico findings, should prompt further studies, to clarify the mode of action, safety, and efficacy of these compounds as mTOR inhibitors.
    Matched MeSH terms: Cell Line, Tumor
  10. A preliminary study of the effects of an extract of Ligularia fischeri leaves on type II collagen-induced arthritis in DBA/1J mice
    Choi EM, Kim YH
    Food Chem Toxicol, 2008 Jan;46(1):375-9.
    PMID: 17904263 DOI: 10.1016/j.fct.2007.08.018
    The present study was undertaken to determine whether Ligularia fischeri leaf extract (LF) is efficacious against collagen-induced arthritis (CIA) in mice. DBA/1J mice were immunized with bovine type II collagen and treated with LF (100 and 200 mg/kg) for 49 days. Mice were assessed regularly for signs of arthritis and the levels of rheumatoid factor, anti-type II collagen antibody, cytokines, AST, ALT, and creatinine in serum were also examined after the animals were killed. The arthritis score and paw edema were markedly suppressed in the groups treated with LF. Moreover, levels of rheumatoid factor, anti-type II collagen antibody, tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 in sera were reduced by LF administration. These data suggest that L. fischeri might be effective for the treatment of inflammatory arthritis like human rheumatoid arthritis.
    Matched MeSH terms: Cell Line
  11. Toxicological evaluation of some Malaysian locally processed raw food products
    Sharif R, Ghazali AR, Rajab NF, Haron H, Osman F
    Food Chem Toxicol, 2008 Jan;46(1):368-74.
    PMID: 17900779
    Malaysian locally processed raw food products are widely used as main ingredients in local cooking. Previous studies showed that these food products have a positive correlation with the incidence of cancer. The cytotoxicity effect was evaluated using MTT assay (3-(4,5-dimetil-2-thiazolil)-2,5-diphenyl-2H-tetrazolium bromide) against Chang liver cells at 2000 microg/ml following 72 h incubation. Findings showed all methanol extracts caused a tremendous drop in the percentage of cell viability at 2000 microg/ml (shrimp paste - 41.69+/-3.36%, salted fish - 37.2+/-1.06%, dried shrimp - 40.32+/-1.8%, p<0.05). To detect DNA damage in a single cell, alkaline Comet Assay was used. None of the extracts caused DNA damage to the Chang liver cells at 62.5 microg/ml following 24 h incubation, as compared to the positive control, hydrogen peroxide (tail moment - 9.50+/-1.50; tail intensity - 30.50+/-2.50). Proximate analysis which was used for the evaluation of macronutrients in food showed that shrimp paste did not comply with the protein requirement (<25%) as in Food Act 1983. Salt was found in every sample with the highest percentage being detected in shrimp paste which exceeded 20%. Following heavy metal analysis (arsenic, cadmium, lead and mercury), arsenic was found in every sample with dried shrimps showing the highest value as compared to the other samples (6.16 mg/kg). In conclusion, several food extracts showed cytotoxic effect but did not cause DNA damage against Chang liver cells. Salt was found as the main additive and arsenic was present in every sample, which could be the probable cause of the toxicity effects observed.
    Matched MeSH terms: Cell Line
  12. Evaluation of Tualang honey as a supplement to fetal bovine serum in cell culture
    Kannan TP, Ali AQ, Abdullah SF, Ahmad A
    Food Chem Toxicol, 2009 Jul;47(7):1696-702.
    PMID: 19394390 DOI: 10.1016/j.fct.2009.04.020
    The aim of this study was to evaluate Tualang honey as a supplement to fetal bovine serum in cell cultures using MTT assay, chromosome aberration test and gene expression analyses. The MTT assay showed the highest percentage of cell proliferation (105.3% increment than control) of human osteoblast cell line (CRL 1543) in 0.0195% honey in Dulbecco's modified eagle medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. There was enhanced cell proliferation corresponding to the decrease in concentrations of honey as indicated by the mitotic index values when the osteoblast cell line was incubated at 37 degrees C for 48 hours. There were no chromosome aberrations both in the honey treated as well as distilled water treated (negative control) cell lines. In the case of gene expression analyses, fibroblast cell lines (CCL 171) were treated with honey (0.0195%) for 24 and 48 hours separately. Though there was over expression for the bcl-xl gene at both 24 and 48 hours, under expression for bcl-xs gene at 24 hours and over expression at 48 hours and under expression for both c-myc and p53 genes at both 24 and 48 hours, none of them were statistically significant in altering the expression of mRNA.
    Matched MeSH terms: Cell Line
  13. Fulltext Formulation, Characterization and Biological Activity Screening of Sodium Alginate-Gum Arabic Nanoparticles Loaded with Curcumin
    Hassani A, Mahmood S, Enezei HH, Hussain SA, Hamad HA, Aldoghachi AF, et al.
    Molecules, 2020 May 10;25(9).
    PMID: 32397633 DOI: 10.3390/molecules25092244
    The approach of drug delivery systems emphasizes the use of nanoparticles as a vehicle, offering the optional property of delivering drugs as a single dose rather than in multiple doses. The current study aims to improve antioxidant and drug release properties of curcumin loaded gum Arabic-sodium alginate nanoparticles (Cur/ALG-GANPs). The Cur/ALG-GANPs were prepared using the ionotropic gelation technique and further subjected to physico-chemical characterization using attenuated total reflectance-Fourier transform infrared (ATR-FTIR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), size distribution, and transmission electron microscopy (TEM). The size of Cur/ALG-GANPs ranged between 10 ± 0.3 nm and 190 ± 0.1 nm and the zeta potential was -15 ± 0.2 mV. The antioxidant study of Cur/ALG-GANPs exhibited effective radical scavenging capacity for 1,1-diphenyl-2-picrylhydrazyl (DPPH) at concentrations that ranged between 30 and 500µg/mL. Cytotoxicity was performed using MTT assay to measure their potential in inhibiting the cell growth and the result demonstrated a significant anticancer activity of Cur/ALG-GANPs against human liver cancer cells (HepG2) than in colon cancer (HT29), lung cancer (A549) and breast cancer (MCF7) cells. Thus, this study indicates that Cur/ALG-GANPs have promising anticancer properties that might aid in future cancer therapy.
    Matched MeSH terms: Cell Line, Tumor
  14. Transcriptome analysis reveals the molecular mechanisms of combined gamma-tocotrienol and hydroxychavicol in preventing the proliferation of 1321N1, SW1783, and LN18 glioma cancer cells
    Abdul Rahman A, Mokhtar NM, Harun R, Jamal R, Wan Ngah WZ
    J Physiol Biochem, 2019 Nov;75(4):499-517.
    PMID: 31414341 DOI: 10.1007/s13105-019-00699-z
    Gamma-tocotrienol (GTT) and hydroxychavicol (HC) exhibit anticancer activity in glioma cancer cells, where the combination of GTT + HC was shown to be more effective than single agent. The aim of this study was to determine the effect of GTT + HC by measuring the cell cycle progression, migration, invasion, and colony formation of glioma cancer cells and elucidating the changes in gene expression mitigated by GTT + HC that are critical to the chemoprevention of glioma cell lines 1321N1 (grade II), SW1783 (grade III), and LN18 (grade IV) using high-throughput RNA sequencing (RNA-seq). Results of gene expression levels and alternative splicing transcripts were validated by qPCR. Exposure of glioma cancer cells to GTT + HC for 24 h promotes cell cycle arrest at G2M and S phases and inhibits cell migration, invasion, and colony formation of glioma cancer cells. The differential gene expression induced by GTT + HC clustered into response to endoplasmic reticulum (ER) stress, cell cycle regulations, apoptosis, cell migration/invasion, cell growth, and DNA repair. Subnetwork analysis of genes altered by GTT + HC revealed central genes, ATF4 and XBP1. The modulation of EIF2AK3, EDN1, and FOXM1 were unique to 1321N1, while CSF1, KLF4, and FGF2 were unique to SW1783. PLK2 and EIF3A gene expressions were only altered in LN18. Moreover, GTT + HC treatment dynamically altered transcripts and alternative splicing expression. GTT + HC showed therapeutic potential against glioma cancer as evident by the inhibition of cell cycle progression, migration, invasion, and colony formation of glioma cancer cells, as well as the changes in gene expression profiles with key targets in ER unfolded protein response pathway, apoptosis, cell cycle, and migration/invasion.
    Matched MeSH terms: Cell Line, Tumor
  15. Pro-apoptotic carboxamide analogues of natural fislatifolic acid targeting Mcl-1 and Bcl-2
    Gapil Tiamas S, Daressy F, Abou Samra A, Bignon J, Steinmetz V, Litaudon M, et al.
    Bioorg Med Chem Lett, 2020 04 01;30(7):127003.
    PMID: 32035700 DOI: 10.1016/j.bmcl.2020.127003
    A library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involved a bio-inspired Diels-Alder cycloaddition, followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1 and Bcl-2 proteins. In this series of cyclohexenyl chalcone analogues, six compounds behaved as dual Bcl-xL/Mcl-1 inhibitors in micromolar range and one exhibited sub-micromolar affinities toward Mcl-1 and Bcl-2. The most potent compounds evaluated on A549 and MCF7 cancer cell lines showed moderate cytotoxicities.
    Matched MeSH terms: Cell Line, Tumor
  16. Fulltext Targeted PDT agent eradicates TrkC expressing tumors via photodynamic therapy (PDT)
    Kue CS, Kamkaew A, Lee HB, Chung LY, Kiew LV, Burgess K
    Mol Pharm, 2015 Jan 5;12(1):212-22.
    PMID: 25487316 DOI: 10.1021/mp5005564
    This contribution features a small molecule that binds TrkC (tropomyosin receptor kinase C) receptor that tends to be overexpressed in metastatic breast cancer cells but not in other breast cancer cells. A sensitizer for (1)O2 production conjugated to this structure gives 1-PDT for photodynamic therapy. Isomeric 2-PDT does not bind TrkC and was used as a control throughout; similarly, TrkC- cancer cells were used to calibrate enhanced killing of TrkC+ cells. Ex vivo, 1- and 2-PDT where only cytotoxic when illuminated, and 1-PDT, gave higher cell death for TrkC+ breast cancer cells. A 1 h administration-to-illumination delay gave optimal TrkC+/TrkC--photocytotoxicity, and distribution studies showed the same delay was appropriate in vivo. In Balb/c mice, a maximum tolerated dose of 20 mg/kg was determined for 1-PDT. 1- and 2-PDT (single, 2 or 10 mg/kg doses and one illumination, throughout) had similar effects on implanted TrkC- tumors, and like those of 2-PDT on TrkC+ tumors. In contrast, 1-PDT caused dramatic TrkC+ tumor volume reduction (96% from initial) relative to the TrkC- tumors or 2-PDT in TrkC+ models. Moreover, 71% of the mice treated with 10 mg/kg 1-PDT (n = 7) showed full tumor remission and survived until 90 days with no metastasis to key organs.
    Matched MeSH terms: Cell Line, Tumor
  17. Nanoglue: an alternative way to display cell-internalizing peptide at the spikes of hepatitis B virus core nanoparticles for cell-targeting delivery
    Lee KW, Tey BT, Ho KL, Tejo BA, Tan WS
    Mol Pharm, 2012 Sep 4;9(9):2415-23.
    PMID: 22775561 DOI: 10.1021/mp200389t
    Cell-internalizing peptides (CIPs) can be used to mediate specific delivery of nanoparticles across cellular membrane. The objective of this study was to develop a display technique using hepatitis B virus (HBV) capsid-binding peptide as a "nanoglue" to present CIPs on HBV nanoparticles for cell-targeting delivery. A CIP was selected from a phage display library and cross-linked specifically at the tips of the spikes of the HBV capsid nanoparticle via the "nanoglue" by using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysulfosuccinimide (sulfo-NHS). Fluorescent oligonucleotides packaged in the nanoparticles and the fluorescein molecules conjugated on the nanoparticles were delivered to cells by using this display technique. This study demonstrated a proof of principle for cell-targeting delivery via "nanoglue" bioconjugation.
    Matched MeSH terms: Cell Line, Tumor
  18. Doxorubicin and siRNA Codelivery via Chitosan-Coated pH-Responsive Mixed Micellar Polyplexes for Enhanced Cancer Therapy in Multidrug-Resistant Tumors
    Butt AM, Amin MC, Katas H, Abdul Murad NA, Jamal R, Kesharwani P
    Mol Pharm, 2016 12 05;13(12):4179-4190.
    PMID: 27934479
    This study investigated the potential of chitosan-coated mixed micellar nanocarriers (polyplexes) for codelivery of siRNA and doxorubicin (DOX). DOX-loaded mixed micelles (serving as cores) were prepared by thin film hydration method and coated with chitosan (CS, serving as outer shell), and complexed with multidrug resistance (MDR) inhibiting siRNA. Selective targeting was achieved by folic acid conjugation. The polyplexes showed pH-responsive enhanced DOX release in acidic tumor pH, resulting in higher intracellular accumulation, which was further augmented by downregulation of mdr-1 gene after treatment with siRNA-complexed polyplexes. In vitro cytotoxicity assay demonstrated an enhanced cytotoxicity in native 4T1 and multidrug-resistant 4T1-mdr cell lines, compared to free DOX. Furthermore, in vivo, polyplexes codelivery resulted in highest DOX accumulation and significantly reduced the tumor volume in mice with 4T1 and 4T1-mdr tumors as compared to the free DOX groups, leading to improved survival times in mice. In conclusion, codelivery of siRNA and DOX via polyplexes has excellent potential as targeted drug nanocarriers for treatment of MDR cancers.
    Matched MeSH terms: Cell Line, Tumor
  19. 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 Line, Tumor
  20. Fulltext Gastroprotective activity of a novel Schiff base derived dibromo substituted compound against ethanol-induced acute gastric lesions in rats
    Saremi K, Rad SK, Tayeby F, Abdulla MA, Karimian H, Majid NA
    BMC Pharmacol Toxicol, 2019 Feb 15;20(1):13.
    PMID: 30770761 DOI: 10.1186/s40360-019-0292-z
    BACKGROUND: Basic function of bromine in body is to activate pepsin production in gastritis with low acidity. The present study encompasses a broad in vivo study to evaluate gastroprotective activity of a novel dibromo substituted Schiff base complex against Sprague Dawley (SD) rats.

    METHODS: 2, 2'-[1, 2-cyclohexanediylbis (nitriloethylidyne)]bis(4-bromophenol) (CNBP) is synthesized via a Schiff base reaction, using the related ketone and diamine as the starting materials. SD rats are divided as normal, ulcer control (5 ml/kg of 10% Tween 20), testing (10 and 20 mg/kg of CNBP) and reference groups (omeprazole 20 mg/kg). Except for the normal group, the rest of the groups are induced gastric ulcer by ethanol 1 h after the pre-treatment. Ulcer area, gastric wall mucus, and acidity of gastric content of the animal stomachs are measured after euthanization. Antioxidant activity of the compound is tested by Ferric reducing antioxidant power (FRAP) test and safety of the compound is identified through acute toxicity by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, activities of superoxide dismutase (SOD), catalase (CAT), levels of prostaglandins E2 (PGE2) and also malondialdehyde (MDA) are determined.

    RESULTS: Antioxidant activity of CNBP was approved via FRAP assay. Vast shallow hemorrhagic injury of gastric glandular mucosa was observed in the ulcer group compared to the CNBP-treated animals. Histological evaluations confirmed stomach epithelial defense effect of CNBP with drastic decrease of gastric ulceration, edema and leucocytes penetration of submucosal stratum. Immunostaining exhibited over-expression in HSP70 protein in CNBP-treated groups compared to that of the ulcer group. Also, gastric protein analysis showed low levels of MDA, PGE2 and high activity of SOD and CAT.

    CONCLUSIONS: CNBP with noticeable antioxidant property showed gastroprotective activity in the testing rodents via alteration of HSP70 protein expression. Also, antioxidant enzyme activities which were changed after treatment with CNBP in the animals could be elucidated as its gastroprotective properties.

    Matched MeSH terms: Cell Line
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