Displaying publications 541 - 560 of 1781 in total

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  1. Fulltext A study on volatile organic compounds emitted by in-vitro lung cancer cultured cells using gas sensor array and SPME-GCMS
    Thriumani R, Zakaria A, Hashim YZH, Jeffree AI, Helmy KM, Kamarudin LM, et al.
    BMC Cancer, 2018 04 02;18(1):362.
    PMID: 29609557 DOI: 10.1186/s12885-018-4235-7
    BACKGROUND: Volatile organic compounds (VOCs) emitted from exhaled breath from human bodies have been proven to be a useful source of information for early lung cancer diagnosis. To date, there are still arguable information on the production and origin of significant VOCs of cancer cells. Thus, this study aims to conduct in-vitro experiments involving related cell lines to verify the capability of VOCs in providing information of the cells.

    METHOD: The performances of e-nose technology with different statistical methods to determine the best classifier were conducted and discussed. The gas sensor study has been complemented using solid phase micro-extraction-gas chromatography mass spectrometry. For this purpose, the lung cancer cells (A549 and Calu-3) and control cell lines, breast cancer cell (MCF7) and non-cancerous lung cell (WI38VA13) were cultured in growth medium.

    RESULTS: This study successfully provided a list of possible volatile organic compounds that can be specific biomarkers for lung cancer, even at the 24th hour of cell growth. Also, the Linear Discriminant Analysis-based One versus All-Support Vector Machine classifier, is able to produce high performance in distinguishing lung cancer from breast cancer cells and normal lung cells.

    CONCLUSION: The findings in this work conclude that the specific VOC released from the cancer cells can act as the odour signature and potentially to be used as non-invasive screening of lung cancer using gas array sensor devices.

    Matched MeSH terms: Cell Line, Tumor
  2. Fulltext Melicope ptelefolia leaf extracts exhibit antioxidant activity and exert anti-proliferative effect with apoptosis induction on four different cancer cell lines
    Kabir MF, Mohd Ali J, Abolmaesoomi M, Hashim OH
    BMC Complement Altern Med, 2017 May 05;17(1):252.
    PMID: 28476158 DOI: 10.1186/s12906-017-1761-9
    BACKGROUND: Melicope ptelefolia is a well-known herb in a number of Asian countries. It is often used as vegetable salad and traditional medicine to address various ailments. However, not many studies have been currently done to evaluate the medicinal benefits of M. ptelefolia (MP). The present study reports antioxidant, anti-proliferative, and apoptosis induction activities of MP leaf extracts.

    METHOD: Young MP leaves were dried, powdered and extracted sequentially using hexane (HX), ethyl acetate (EA), methanol (MeOH) and water (W). Antioxidant activity was evaluated using ferric reducing antioxidant power (FRAP), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) radicals scavenging and cellular antioxidant activity (CAA) assays. Anti-proliferative activity was evaluated through cell viability assay, using the following four human cancer cell lines: breast (HCC1937, MDA-MB-231), colorectal (HCT116) and liver (HepG2). The anti-proliferative activity was further confirmed through cell cycle and apoptosis assays, including annexin-V/7-aminoactinomycin D staining and measurements of caspase enzymes activation and inhibition.

    RESULT: Overall, MP-HX extract exhibited the highest antioxidant potential, with IC50 values of 267.73 ± 5.58 and 327.40 ± 3.80 μg/mL for ABTS and DPPH radical-scavenging assays, respectively. MP-HX demonstrated the highest CAA activity in Hs27 cells, with EC50 of 11.30 ± 0.68 μg/mL, while MP-EA showed EC50 value of 37.32 ± 0.68 μg/mL. MP-HX and MP-EA showed promising anti-proliferative activity towards the four cancer cell lines, with IC50 values that were mostly below 100 μg/mL. MP-HX showed the most notable anti-proliferative activity against MDA-MB-231 (IC50 = 57.81 ± 3.49 μg/mL) and HCT116 (IC50 = 58.04 ± 0.96 μg/mL) while MP-EA showed strongest anti-proliferative activity in HCT116 (IC50 = 64.69 ± 0.72 μg/mL). The anticancer potential of MP-HX and MP-EA were also demonstrated by their ability to induce caspase-dependent apoptotic cell death in all of the cancer cell lines tested. Cell cycle analysis suggested that both the MP-HX and MP-EA extracts were able to disrupt the cell cycle in most of the cancer cell lines.

    CONCLUSIONS: MP-HX and MP-EA extracts demonstrated notable antioxidant, anti-proliferative, apoptosis induction and cancer cell cycle inhibition activities. These findings reflect the promising potentials of MP to be a source of novel phytochemical(s) with health promoting benefits that are also valuable for nutraceutical industry and cancer therapy.

    Matched MeSH terms: Cell Line, Tumor
  3. Identification and comparison of RCMV ALL 03 open reading frame (ORF) among several different strains of cytomegalovirus worldwide
    Balakrishnan KN, Abdullah AA, Bala J, Abba Y, Sarah SA, Jesse FFA, et al.
    Infect Genet Evol, 2017 10;54:81-90.
    PMID: 28642159 DOI: 10.1016/j.meegid.2017.06.020
    BACKGROUND: Rat cytomegalovirus ALL-03 (Malaysian strain) which was isolated from a placenta and uterus of a house rat, Rattus rattus diardii has the ability to cross the placenta and infecting the fetus. To further elucidate the pathogenesis of the Malaysian strain of Rat Cytomegalovirus ALL-03 (RCMV ALL-03), detailed analysis on the viral genome sequence is crucial.

    METHODS: Genome sequencing of RCMV ALL-03 was carried out in order to identify the open reading frame (ORF), homology comparison of ORF with other strains of CMV, phylogenetic analysis, classifying ORF with its corresponding conserved genes, and determination of functional proteins and grouping of gene families in order to obtain fundamental knowledge of the genome.

    RESULTS: The present study revealed a total of 123 Coding DNA sequences (CDS) from RCMV ALL-03 with 37 conserved ORF domains as with all herpesvirus genomes. All the CDS possess similar function with RCMV-England followed by RCMV-Berlin, RCMV-Maastricht, and Human CMV. The phylogenetic analysis of RCMV ALL-03 based on conserving genes of herpes virus showed that the Malaysian RCMV isolate is closest to RCMV-English and RCMV-Berlin strains, with 99% and 97% homology, respectively. Similarly, it also demonstrated an evolutionary relationship between RCMV ALL-03 and other strains of herpesviruses from all the three subfamilies. Interestingly, betaherpesvirus subfamily, which has been shown to be more closely related with gammaherpesviruses as compared to alphaherpesviruses, shares some of the functional ORFs. In addition, the arrangement of gene blocks for RCMV ALL-03, which was conserved among herpesvirus family members was also observed in the RCMV ALL-03 genome.

    CONCLUSION: Genomic analysis of RCMV ALL-03 provided an overall picture of the whole genome organization and it served as a good platform for further understanding on the divergence in the family of Herpesviridae.

    Matched MeSH terms: Cell Line
  4. In vitro neuroprotective effects of naringenin nanoemulsion against β-amyloid toxicity through the regulation of amyloidogenesis and tau phosphorylation
    Md S, Gan SY, Haw YH, Ho CL, Wong S, Choudhury H
    Int J Biol Macromol, 2018 Oct 15;118(Pt A):1211-1219.
    PMID: 30001606 DOI: 10.1016/j.ijbiomac.2018.06.190
    Alzheimer's disease (AD) is an increasingly prevalent neurological disorder of the central nervous system. There is growing evidence that amyloidogenesis is a pathological hallmark for AD; this leads to the formation of senile plaques. Naringenin is a bioflavonoid which has neuroprotective effects through its antioxidant and anti-inflammatory properties. However, its clinical usage is limited due to its inefficient transport across biological membranes. In the present study, a naringenin nanoemulsion was prepared and its neuroprotective effects were tested against β-amyloid induced neurotoxicity in a human neuroblastoma cell line (SH-SY5Y). The optimised, naringenin-loaded nanoemulsion formulation had a droplet size of 113.83 ± 3.35 nm and around 50 nm, as assessed respectively by photon correlation spectroscopy and transmission electron microscopy. The preparation showed a low polydispersity index (0.312 ± 0.003), a high zeta potential (12.4 ± 1.05) and a high percentage transmittance (97.01%). The neuroprotective activity of naringenin nanoemulsions was determined by assessing their ability to protect SH-SY5Y neuroblastoma cells against the neurotoxic effect of beta amyloid (Aβ). Aβ-induced production of reactive oxygen species (ROS), amyloid precursor protein (APP), β-secretase (BACE), total tau and phosphorylated tau (pT231) was also determined. The naringenin loaded nanoemulsion significantly alleviated the direct neurotoxic effects of Aβ on SH-SY5Y cells; this was associated with a down-regulation of APP and BACE expression, indicating reduced amyloidogenesis. Furthermore, it decreased the levels of phosphorylated tau in SH-SY5Y cells exposed to Aβ. These results suggest that a naringenin-loaded nanoemulsion could be a promising agent for the treatment of Alzheimer's disease.
    Matched MeSH terms: Cell Line, Tumor
  5. Silver nanoparticle functionalized CS-g-(CA-MA-PZA) carrier for sustainable anti-tuberculosis drug delivery
    Amarnath Praphakar R, Jeyaraj M, Ahmed M, Suresh Kumar S, Rajan M
    Int J Biol Macromol, 2018 Oct 15;118(Pt B):1627-1638.
    PMID: 29981824 DOI: 10.1016/j.ijbiomac.2018.07.008
    Recently, drug functionalized biodegradable polymers have been appreciated to be imperative to fabricate multi-drug delivery nanosystems for sustainable drug release. In this work, amphiphilic chitosan-grafted-(cetyl alcohol-maleic anhydride-pyrazinamide) (CS-g-(CA-MA-PZA)) was synthesized by multi-step reactions. The incorporation of rifampicin (RF) and entrapment of silver nanoparticles (Ag NPs) on CS-g-(CA-MA-PZA) polymer was carried out by dialysis technique. From the FT-IR experiment, the polymer modification, incorporation of drugs and the entrapment of Ag NPs on micelles were confirmed. The surface morphology of Ag NPs, polymeric system and drug loaded micelles was described by SEM, TEM and AFM techniques. In addition, the controlled release behaviour of CS-g-(CA-MA-PZA) micelles was studied by UV-Vis spectroscopy. In vitro cell viability, cell apoptosis and cellular uptake experiments shows that multi-drug delivery system could enhance the biocompatibility and higher the cytotoxicity effect on the cells. Since the prepared amphiphilic polymeric micelles exhibit spotty features and the system is a promising strategy for a novel candidate for immediate therapeutically effects for alveolar macrophages.
    Matched MeSH terms: Cell Line
  6. Differential effects of two-pore channel protein 1 and 2 silencing in MDA-MB-468 breast cancer cells
    Jahidin AH, Stewart TA, Thompson EW, Roberts-Thomson SJ, Monteith GR
    Biochem Biophys Res Commun, 2016 Sep 02;477(4):731-736.
    PMID: 27353380 DOI: 10.1016/j.bbrc.2016.06.127
    Two-pore channel proteins, TPC1 and TPC2, are calcium permeable ion channels found localized to the membranes of endolysosomal calcium stores. There is increasing interest in the role of TPC-mediated intracellular signaling in various pathologies; however their role in breast cancer has not been extensively evaluated. TPC1 and TPC2 mRNA was present in all non-tumorigenic and tumorigenic breast cell lines assessed. Silencing of TPC2 but not TPC1 attenuated epidermal growth factor-induced vimentin expression in MDA-MB-468 breast cancer cells. This effect was not due to a general inhibition of epithelial to mesenchymal transition (EMT) as TPC2 silencing had no effect on epidermal growth factor (EGF)-induced changes on E-cadherin expression. TPC1 and TPC2 were also shown to differentially regulate cyclopiazonic acid (CPA)-mediated changes in cytosolic free Ca(2+). These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells.
    Matched MeSH terms: Cell Line, Tumor
  7. DNA Nanostructures Carrying Stoichiometrically Definable Antibodies
    Setyawati MI, Kutty RV, Leong DT
    Small, 2016 Oct;12(40):5601-5611.
    PMID: 27571230 DOI: 10.1002/smll.201601669
    Targeted drug delivery is one of the key challenges in cancer nanomedicine. Stoichiometric and spatial control over the antibodies placement on the nanomedicine vehicle holds a pivotal role to overcome this key challenge. Here, a DNA tetrahedral is designed with available conjugation sites on its vertices, allowing to bind one, two, or three cetuximab antibodies per DNA nanostructure. This stoichiometrically definable cetuximab conjugated DNA nanostructure shows enhanced targeting on the breast cancer cells, which results with higher overall killing efficacy of the cancer cells.
    Matched MeSH terms: Cell Line, Tumor
  8. Design and development of dry powder sulfobutylether-β-cyclodextrin complex for pulmonary delivery of fisetin
    Mohtar N, Taylor KM, Sheikh K, Somavarapu S
    Eur J Pharm Biopharm, 2017 Apr;113:1-10.
    PMID: 27916704 DOI: 10.1016/j.ejpb.2016.11.036
    This study has investigated complexation of fisetin, a natural flavonoid, with three types of cyclodextrins to improve its solubility. Sulfobutylether-β-cyclodextrin (SBE-β-CD) showed the highest complexation efficiency while maintaining the in vitro antioxidant activity of fisetin. Addition of 20%v/v ethanol in water improved the amount of solubilized fisetin in the complex 5.9-fold compared to the system containing water alone. Spray drying of fisetin-SBE-β-CD complex solution in the presence of ethanol produced a dry powder with improved aerosolization properties when delivered from a dry powder inhaler, indicated by a 2-fold increase in the fine particle fraction (FPF) compared to the powder produced from the complex solution containing water alone. The pitted morphological surface of these particles suggested a more hollow internal structure, indicating a lighter and less dense powder. Incorporation of 20%w/w leucine improved the particle size distribution of the powder and further increased the FPF by 2.3-fold. This formulation also showed an EC50 value equivalent to fisetin alone in the A549 cell line. In conclusion, an inhalable dry powder containing fisetin-SBE-β-CD complex was successfully engineered with an improved aqueous solubility of fisetin. The dry powder may be useful to deliver high amounts of fisetin to the deep lung region for therapeutic purposes.
    Matched MeSH terms: Cell Line, Tumor
  9. Fulltext Stem cell therapy as a potential treatment for glaucoma
    Kamal, M., Amini, F., Ramasamy, TS
    JUMMEC, 2016;19(1):23-32.
    MyJurnal
    Glaucoma is a common eye disease that can cause irreversible damage if left undiagnosed and untreated. It is one of the most common neurodegenerative diseases causing blindness. Pre-clinical studies have been carried out on animal models of glaucoma for stem cell therapy. We carried out a systematic review to determine whether stem cell therapy had the potential to treat glaucoma. Nine studies were selected based on the predetermined inclusion and exclusion criteria. Of these nine studies, eight focused on neuroprotection conferred by stem cells, and the remaining one on neuroregeneration. Results from these studies showed that there was a potential in stem cell based therapy in treating glaucoma, especially regarding neuroprotection via neurotrophic factors. The studies revealed that a brain-derived neurotrophic factor expressed by stem cells promoted the survival of retinal ganglion cells in murine glaucoma models. The transplanted cells survived without any side effects. While these studies proved that stem cells provided neuroprotection in glaucoma, improvement of vision could not be determined. Clinical studies would be required to determine whether the protection of RGC correlated with improvement in visual function. Furthermore, these murine studies could not be translated into clinical therapy due to the heterogeneity of the experimental methods and the
    use of different cell lines. In conclusion, the use of stem cells in the clinical therapy of glaucoma will be an important step in the future as it will transform present-day treatment with the hope of restoring sight to patients with glaucoma.
    Matched MeSH terms: Cell Line
  10. Modified porous scaffolds of silk fibroin with mimicked microenvironment based on decellularized pulp/fibronectin for designed performance biomaterials in maxillofacial bone defect
    Sangkert S, Kamonmattayakul S, Chai WL, Meesane J
    J Biomed Mater Res A, 2017 Jun;105(6):1624-1636.
    PMID: 28000362 DOI: 10.1002/jbm.a.35983
    Maxillofacial bone defect is a critical problem for many patients. In severe cases, the patients need an operation using a biomaterial replacement. Therefore, to design performance biomaterials is a challenge for materials scientists and maxillofacial surgeons. In this research, porous silk fibroin scaffolds with mimicked microenvironment based on decellularized pulp and fibronectin were created as for bone regeneration. Silk fibroin scaffolds were fabricated by freeze-drying before modification with three different components: decellularized pulp, fibronectin, and decellularized pulp/fibronectin. The morphologies of the modified scaffolds were observed by scanning electron microscopy. Existence of the modifying components in the scaffolds was proved by the increase in weights and from the pore size measurements of the scaffolds. The modified scaffolds were seeded with MG-63 osteoblasts and cultured. Testing of the biofunctionalities included cell viability, cell proliferation, calcium content, alkaline phosphatase activity (ALP), mineralization and histological analysis. The results demonstrated that the modifying components organized themselves into aggregations of a globular structure. They were arranged themselves into clusters of aggregations with a fibril structure in the porous walls of the scaffolds. The results showed that modified scaffolds with a mimicked microenvironment of decellularized pulp/fibronectin were suitable for cell viability since the cells could attach and spread into most of the pores of the scaffold. Furthermore, the scaffolds could induce calcium synthesis, mineralization, and ALP activity. The results indicated that modified silk fibroin scaffolds with a mimicked microenvironment of decellularized pulp/fibronectin hold promise for use in tissue engineering in maxillofacial bone defects. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1624-1636, 2017.
    Matched MeSH terms: Cell Line
  11. Fulltext The neutralizing role of IgM during early Chikungunya virus infection
    Chua CL, Sam IC, Chiam CW, Chan YF
    PLoS One, 2017;12(2):e0171989.
    PMID: 28182795 DOI: 10.1371/journal.pone.0171989
    The antibody isotype IgM appears earlier than IgG, within days of onset of symptoms, and is important during the early stages of the adaptive immune response. Little is known about the functional role of IgM during infection with chikungunya virus (CHIKV), a recently reemerging arbovirus that has caused large global outbreaks. In this study, we studied antibody responses in 102 serum samples collected during CHIKV outbreaks in Malaysia. We described the neutralizing role of IgM at different times post-infection and examined the independent contributions of IgM and IgG towards the neutralizing capacity of human immune sera during the early phase of infection, including the differences in targets of neutralizing epitopes. Neutralizing IgM starts to appear as early as day 4 of symptoms, and their appearance from day 6 is associated with a reduction in viremia. IgM acts in a complementary manner with the early IgG, but plays the main neutralizing role up to a point between days 4 and 10 which varies between individuals. After this point, total neutralizing capacity is attributable almost entirely to the robust neutralizing IgG response. IgM preferentially binds and targets epitopes on the CHIKV surface E1-E2 glycoproteins, rather than individual E1 or E2. These findings provide insight into the early antibody responses to CHIKV, and have implications for design of diagnostic serological assays.
    Matched MeSH terms: Cell Line
  12. Fulltext Optimization of monoclonal antibodies purification expressed in H-192 cells using preparative native-polyacrylamide gel electrophoresis
    Krishnan, Santhana, Mimi Sakinah Abdul Munaim, Zularisam Abdul Wahid, Chua, Yeo Gek Kee, Chew, Few Nee
    Journal of Biochemistry, Microbiology and Biotechnology, 2015;3(1):21-25.
    MyJurnal
    Monoclonal antibodies (mAbs) are unique and specific drug molecules targeting the treatment of various diseases such as arthritis, immune disorders, infectious diseases, and cancer etc. Different methods such as antibody coupled affinity chromatography, hydrophobic interaction chromatography, etc., can be applied to purify mAbs from various sources. This article provides a simple, cost effective, preparative native-polyacrylamide gel electrophoresis (n-PAGE)technique to purify mAbs expressed in H-192 cells (Hybridoma murine cell lines) against an antigen i.e. 17-alpha-hydroxyprogesterone (17-OHP), which further can have diagnostic application to detect Congenital Adrenal Hyperplasia (CAH). Furthermore, different parameters such as concentration and volume of the feedstock (medium containing antibodies), pore size of gel, height of resolving gel etc. were optimized to obtain the maximum purity and yield of mAbs.
    Matched MeSH terms: Cell Line
  13. Fulltext Synthesis, characterisation and biological activities of Ru(III), Mo(V), Cd(II), Zn(II) and Cu(II) complexes containing a novel Nitrogen-Sulphur Macrocyclic Schiff base derived from Glyoxal
    Chah, C.K., Ravoof, T.B.S.A., Veerakumarasivam, A.
    Pertanika Journal of Science & Technology, 2018;26(2):653-670.
    MyJurnal
    A novel nitrogen-sulphur macrocyclic Schiff base, 4,11,20,27-tetrathioxo3,12,19,28-tetrathia-5,6,9,10,21,22,25,26-octaazatricyclo[28.2.2.214,17]hexatriaconta 1(33),6,8,14(36),15,17(35),22,24,30(34),31-decaene-2,13,18,29-tetraone (TGSB) derived from terephthaloyl-bis-dithiocarbazate (TDTC) and glyoxal (ethane-1,2-dione) is synthesised via condensation. Metal complexes are formed by reacting the Schiff base with various metal salts such as Ru(III), Mo(V), Cd(II), Zn(II) and Cu(II). The complexes are expected to have a general formula of M2L or M3L with a square planar or square pyramidal geometry. These compounds were characterised by various physicochemical and spectroscopic techniques. From the data, it is concluded that the azomethine nitrogen atom and the thiolate sulphur atom from the ligand are bonded to the metal ion. In the IR spectra of the complexes, the presence of the C=N band in the region of 1600 cm-1 indicates the successful formation of the Schiff base. The structures of the Schiff base and metal complexes are confirmed via FT-IR, GC-MS and NMR spectroscopic analysis. The magnetic susceptibility measurements, electronic spectral data and molar conductivity analysis support the desired geometry of the complexes. The Schiff base and its metal complexes are evaluated for their biological activities against the invasive human bladder carcinoma cell line (EJ-28) and the minimuminvasive human bladder carcinoma cell line (RT-112). The RuTGSB and CdTGSB complexes showed selective activity against RT-112.
    Matched MeSH terms: Cell Line
  14. Fulltext Cycloartane triterpenoid (23R, 24E)-23-acetoxymangiferonic acid inhibited proliferation and migration in B16-F10 melanoma via MITF downregulation caused by inhibition of both β-catenin and c-Raf-MEK1-ERK signaling axis
    Kaneda T, Matsumoto M, Sotozono Y, Fukami S, Nugroho AE, Hirasawa Y, et al.
    J Nat Med, 2019 Jan;73(1):47-58.
    PMID: 30084054 DOI: 10.1007/s11418-018-1233-7
    We recently reported that (23R, 24E)-23-acetoxymangiferonic acid (23R-AMA), a cycloartane triterpenoid isolated by activity-guided separation from a methanol extract of Garcinia sp. bark, inhibited melanin production via inhibition of tyrosinase (TYR) expression in the B16-F10 melanoma cell line. Since 23R-AMA also inhibited microphthalmia-associated transcription factor (MITF) expression, an upstream factor of TYR, these features of 23R-AMA were thought to be appropriate for development of whitening cosmetics. However, 23R-AMA exhibited growth inhibition other than inhibition of melanin production in B16-F10 cells. Therefore, we investigated biological activities of 23R-AMA in detail, focused on its application as an anti-melanoma compound. In this study, we demonstrated that 23R-AMA inhibited cell proliferation and basic FGF (bFGF)-induced migration in B16-F10 cells. Furthermore, 23R-AMA promoted ser45/thr41 phosphorylation of β-catenin and suppressed its intranuclear accumulation, which was suggested to be related to inhibition of MITF expression. The transcriptional activity of MITF is known to be regulated by phosphorylation via activated ERK. Further investigation revealed that 23R-AMA inhibited phosphorylation of c-Raf, MEK-1, and ERK, and also that of upstream molecules including FAK and c-Src. These results suggested that 23R-AMA inhibited growth and migration of B16-F10 melanoma by regulating both MITF expression and its activity. The activities of 23R-AMA reported in this study are new aspects of cycloartane triterpenoids.
    Matched MeSH terms: Cell Line, Tumor
  15. Fisetin induces apoptosis in breast cancer MDA-MB-453 cells through degradation of HER2/neu and via the PI3K/Akt pathway
    Guo G, Zhang W, Dang M, Yan M, Chen Z
    J Biochem Mol Toxicol, 2019 Apr;33(4):e22268.
    PMID: 30431692 DOI: 10.1002/jbt.22268
    Overexpression of human epidermal growth factor receptor 2 (HER2) is observed in breast cancer. The major snag faced by the human population is the development of chemoresistance to HER2 inhibitors by advanced stage breast cancer cells. Moreover, recent researchers focussed on fisetin as an antiproliferative and chemotherapeutic agent. Therefore, this study was intended to analyze the effects of fisetin on HER2/neu-overexpressing breast cancer cell lines. Our results depicted that fisetin induced apoptosis of these cells by various mechanisms, such as inactivation of the receptor, induction of proteasomal degradation, decreasing its half-life, decreasing enolase phosphorylation, and alteration of phosphatidylinositol 3-kinase/Akt signaling.
    Matched MeSH terms: Cell Line, Tumor
  16. Nipah Virus Infection of Immature Dendritic Cells Increases Its Transendothelial Migration Across Human Brain Microvascular Endothelial Cells
    Tiong V, Shu MH, Wong WF, AbuBakar S, Chang LY
    Front Microbiol, 2018;9:2747.
    PMID: 30483242 DOI: 10.3389/fmicb.2018.02747
    Nipah virus (NiV) can infect multiple organs in humans with the central nervous system (CNS) being the most severely affected. Currently, it is not fully understood how NiV spreads throughout the body. NiV has been shown to infect certain leukocyte populations and we hypothesized that these infected cells could cross the blood-brain barrier (BBB), facilitating NiV entry into the CNS. Here, three leukocyte types, primary immature dendritic cells (iDC), primary monocytes (pMO), and monocytic cell line (THP-1), were evaluated for permissiveness to NiV. We found only iDC and THP-1 were permissive to NiV. Transendothelial migration of mock-infected and NiV-infected leukocytes was then evaluated using an in vitro BBB model established with human brain microvascular endothelial cells (HBMEC). There was approximately a threefold increase in migration of NiV-infected iDC across endothelial monolayer when compared to mock-infected iDC. In contrast, migration rates for pMO and THP-1 did not change upon NiV infection. Across TNF-α-treated endothelial monolayer, there was significant increase of almost twofold in migration of NiV-infected iDC and THP-1 over mock-infected cells. Immunofluorescence analysis showed the migrated NiV-infected leukocytes retained their ability to infect other cells. This study demonstrates for the first time that active NiV infection of iDC and THP-1 increased their transendothelial migration activity across HBMEC and activation of HBMEC by TNF-α further promoted migration. The findings suggest that NiV infection of leukocytes to disseminate the virus via the "Trojan horse" mechanism is a viable route of entry into the CNS.
    Matched MeSH terms: Cell Line
  17. Fulltext Design, synthesis and biological evaluation of 3-(2-aminooxazol-5-yl)-2H-chromen-2-one derivatives
    Kakkar S, Kumar S, Lim SM, Ramasamy K, Mani V, Shah SAA, et al.
    Chem Cent J, 2018 Dec 04;12(1):130.
    PMID: 30515643 DOI: 10.1186/s13065-018-0499-x
    BACKGROUND: In view of wide range of biological activities of oxazole, a new series of oxazole analogues was synthesized and its chemical structures were confirmed by spectral data (Proton/Carbon-NMR, IR, MS etc.). The synthesized oxazole derivatives were screened for their antimicrobial and antiproliferative activities.

    RESULTS AND DISCUSSION: The antimicrobial activity was performed against selected fungal and bacterial strains using tube dilution method. The antiproliferative potential was evaluated against human colorectal carcinoma (HCT116) and oestrogen- positive human breast carcinoma (MCF7) cancer cell lines using Sulforhodamine B assay and, results were compared to standard drugs, 5-fluorouracil and tamoxifen, respectively.

    CONCLUSION: The performed antimicrobial activity indicated that compounds 3, 5, 6, 8 and 14 showed promising activity against selected microbial species. Antiproliferative screening found compound 14 to be the most potent compound against HCT116 (IC50 = 71.8 µM), whereas Compound 6 was the most potent against MCF7 (IC50 = 74.1 µM). Further, the molecular docking study has been carried to find out the interaction between active oxazole compounds with CDK8 (HCT116) and ER-α (MCF7) proteins indicated that compound 14 and 6 showed good dock score with better potency within the ATP binding pocket and may be used as a lead for rational drug designing of the anticancer molecule.

    Matched MeSH terms: Cell Line
  18. Report: Cytotoxic activity of phytochemicals from the stem bark of Calophyllum castaneum
    Lim CK, Gan SY, Yi V, Jong M, Leong CO, Mai CW, et al.
    Pak J Pharm Sci, 2019 Sep;32(5):2183-2187.
    PMID: 31813886
    Phytochemical investigation on the dichloromethane stem bark extract of Calophyllum castaneum resulted in the isolation of five compounds, namely isoblancoic acid (1), blancoic acid (2), euxanthone (3), friedelin (4) and friedelinol (5). All these compounds were isolated for the first time from this plant. Their chemical structures were elucidated based on the spectroscopic analyses. The cytotoxicity of compounds 1-5 was assessed on a panel of cancer cell lines including bone (Saos-2, mg63), colorectal (HT29, Caco-2, HCC2998, SW48, HCT116, KM12), liver (HepG2), lung (H1299, Calu-3), and brain (C6), using 5-fluorouracil as positive control. Pronounced antiproliferative activities were observed for compound 1 which exhibited a comparable activity with the positive control, against brain (C6) and colorectal (SW48, KM12, HCT116) cancer cell lines showing IC50 values in the range of 14 to 65μM. Meanwhile, compound 5 displayed a greater cytotoxic effect showing at least 2-fold more strongly than the positive control, against C6 brain cancer cells. The assay findings have unveiled the therapeutic value of phytochemicals from Calophyllum castaneum as anti-cancer agents.
    Matched MeSH terms: Cell Line, Tumor
  19. An amino acid change in nsP4 of chikungunya virus confers fitness advantage in human cell lines rather than in Aedes albopictus
    Fu JYL, Chua CL, Vythilingam I, Sulaiman WYW, Wong HV, Chan YF, et al.
    J Gen Virol, 2019 11;100(11):1541-1553.
    PMID: 31613205 DOI: 10.1099/jgv.0.001338
    Chikungunya virus (CHIKV) has caused large-scale epidemics of fever, rash and arthritis since 2004. This unprecedented re-emergence has been associated with mutations in genes encoding structural envelope proteins, providing increased fitness in the secondary vector Aedes albopictus. In the 2008-2013 CHIKV outbreaks across Southeast Asia, an R82S mutation in non-structural protein 4 (nsP4) emerged early in Malaysia or Singapore and quickly became predominant. To determine whether this nsP4-R82S mutation provides a selective advantage in host cells, which may have contributed to the epidemic, the fitness of infectious clone-derived CHIKV with wild-type nsP4-82R and mutant nsP4-82S were compared in Ae. albopictus and human cell lines. Viral infectivity, dissemination and transmission in Ae. albopictus were not affected by the mutation when the two variants were tested separately. In competition, the nsP4-82R variant showed an advantage over nsP4-82S in dissemination to the salivary glands, but only in late infection (10 days). In human rhabdomyosarcoma (RD) and embryonic kidney (HEK-293T) cell lines coinfected at a 1 : 1 ratio, wild-type nsP4-82R virus was rapidly outcompeted by nsP4-82S virus as early as one passage (3 days). In conclusion, the nsP4-R82S mutation provides a greater selective advantage in human cells than in Ae. albopictus, which may explain its apparent natural selection during CHIKV spread in Southeast Asia. This is an unusual example of a naturally occurring mutation in a non-structural protein, which may have facilitated epidemic transmission of CHIKV.
    Matched MeSH terms: Cell Line
  20. Fulltext Antitumor and antioxidant effects of Clinacanthus nutans Lindau in 4 T1 tumor-bearing mice
    Nik Abd Rahman NMA, Nurliyana MY, Afiqah MNFNN, Osman MA, Hamid M, Lila MAM
    BMC Complement Altern Med, 2019 Nov 29;19(1):340.
    PMID: 31783838 DOI: 10.1186/s12906-019-2757-4
    BACKGROUND: Clinacanthus nutans Lindau (C. nutans) is a species of in Acanthaceae family and primarily used in South East Asian countries. C. nutans is well known as Sabah snake grass in Malaysia, and its leaves have diverse medicinal potential in conventional applications, including cancer treatments. On the basis of literature search, there is less conclusive evidence of the involvement of phytochemical constituents in breast cancer, in particular, animal tumor models. The current study aimed to determine the antitumor and antioxidant activities of C. nutans extract in 4 T1 tumor-bearing mice.

    METHODS: C. nutans leaves were subjected to methanol extraction and divided into two different concentrations, 200 mg/kg (low-dose) and 1000 mg/kg (high-dose). The antitumor effects of C. nutans extracts were assessed using bone marrow smearing, clonogenic, and splenocyte immunotype analyses. In addition, hematoxylin and eosin, tumor weight and tumor volume profiles also used to indicate apoptosis appearance. Serum cytokine levels were examined using ELISA assay. In addition, nitric oxide assay reflecting antioxidant activity was performed.

    RESULTS: From the results obtained, the methanol extract of C. nutans leaves at 200 mg/kg (P cells, tumor weight, and tumor volume. No inflammatory and adverse reactions related to splenocytes activities were found in all treated groups of mice. Despite its promising results, the concentration of both C. nutans extracts have also reduced the number of colonies formed in the liver and lungs.

    CONCLUSION: In conclusion, C. nutans extracts exert antitumor and antioxidant activities against 4 T1 mouse breast model with no adverse effect and inflammatory response at high dose of 1000 mg/kg, indicating an effective and complementary approach for cancer prevention and treatment.

    Matched MeSH terms: Cell Line, Tumor
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