Displaying publications 81 - 100 of 543 in total

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  1. Fulltext Artonin E induces p53-independent G1 cell cycle arrest and apoptosis through ROS-mediated mitochondrial pathway and livin suppression in MCF-7 cells
    Etti IC, Rasedee A, Hashim NM, Abdul AB, Kadir A, Yeap SK, et al.
    Drug Des Devel Ther, 2017;11:865-879.
    PMID: 28356713 DOI: 10.2147/DDDT.S124324
    Artonin E is a prenylated flavonoid compound isolated from the stem bark of Artocarpus elasticus. This phytochemical has been previously reported to be drug-like with full compliance to Lipinski's rule of five and good physicochemical properties when compared with 95% of orally available drugs. It has also been shown to possess unique medicinal properties that can be utilized in view of alleviating most human disease conditions. In this study, we investigated the cytotoxic mechanism of Artonin E in MCF-7 breast cancer cells, which has so far not been reported. In this context, Artonin E significantly suppressed the breast cancer cell's viability while inducing apoptosis in a dose-dependent manner. This apoptosis induction was caspase dependent, and it is mediated mainly through the intrinsic pathway with the elevation of total reactive oxygen species. Gene and protein expression studies revealed significant upregulation of cytochrome c, Bax, caspases 7 and 9, and p21 in Artonin E-treated MCF-7 cells, while MAPK and cyclin D were downregulated. Livin, a member of the inhibitors of apoptosis, whose upregulation has been noted to precede chemotherapeutic resistance and apoptosis evasion was remarkably repressed. In all, Artonin E stood high as a potential agent in the treatment of breast cancer.
    Matched MeSH terms: Cell Proliferation/drug effects
  2. Fulltext Assessment of antioxidant capacity and cytotoxicity of selected Malaysian plants
    Ling LT, Radhakrishnan AK, Subramaniam T, Cheng HM, Palanisamy UD
    Molecules, 2010 Apr;15(4):2139-51.
    PMID: 20428033 DOI: 10.3390/molecules15042139
    Thirteen Malaysian plants; Artocarpus champeden, Azadirachta indica, Fragaria x ananassa, Garcinia mangostana, Lawsonia inermis, Mangifera indica, Nephelium lappaceum, Nephelium mutobile, Peltophorum pterocarpum, Psidium guajava and Syzygium aqueum, selected for their use in traditional medicine, were subjected to a variety of assays. Antioxidant capability, total phenolic content, elemental composition, as well as it cytotoxity to several cell lines of the aqueous and ethanolic extracts from different parts of these selected Malaysian plants were determined. In general, the ethanolic extracts were better free radical scavengers than the aqueous extracts and some of the tested extracts were even more potent than a commercial grape seed preparation. Similar results were seen in the lipid peroxidation inhibition studies. Our findings also showed a strong correlation of antioxidant activity with the total phenolic content. These extracts when tested for its heavy metals content, were found to be below permissible value for nutraceutical application. In addition, most of the extracts were found not cytotoxic to 3T3 and 4T1 cells at concentrations as high as 100 microg/mL. We conclude that although traditionally these plants are used in the aqueous form, its commercial preparation could be achieved using ethanol since a high total phenolic content and antioxidant activity is associated with this method of preparation.
    Matched MeSH terms: Cell Proliferation/drug effects
  3. Fulltext Assessment of genotoxicity and cytotoxicity of standardized aqueous extract from leaves of Erythroxylum cuneatum in human HepG2 and WRL68 cells line
    Wesam RK, Ghanya AN, Mizaton HH, Ilham M, Aishah A
    Asian Pac J Trop Med, 2013 Oct;6(10):811-6.
    PMID: 23870471 DOI: 10.1016/S1995-7645(13)60143-1
    OBJECTIVE: To investigate the cytotoxicity and the genotoxicity of standardized aqueous of dry leaves of Erythroxylum cuneatum (E. cuneatum) in human HepG2 and WRL68 cells.

    METHODS: The cytotoxicity of E. cuneatum extract was evaluated by both MTS and LDH assays. Genotoxicity study on E. cuneatum extract was assessed by the single cell gel electrophoresis (comet assay). The protective effect of E. cuneatum against menadione-induced cytotoxicity was also investigated.

    RESULTS: Results from this study showed that E. cuneatum extract exhibited cytotoxic activities towards the cells with IC50 value of (125±12) and (125±14) μg/mL for HepG2 and WRL68 cells respectively, after 72 h incubation period as determined by MTS assay. LDH leakage was detected at (251±19) and (199.5±12.0) μg/mL for HepG2 and WRL68 respectively. Genotoxicity study results showed that treatment with E. cuneatum up to 1 mg/mL did not cause obvious DNA damage in WRL68 and HepG2 cells. Addition of E. cunaetum did not show significant protection towards menadione in WRL68 and HepG2 Cells.

    CONCLUSIONS: E. cuneatum standardized aqueous extract might be developed in order to establish new pharmacological possibilities for its application.

    Matched MeSH terms: Cell Proliferation/drug effects
  4. Assessment of in vitro antioxidant, antibacterial and immune activation potentials of aqueous and ethanol extracts of Phyllanthus niruri
    Amin ZA, Abdulla MA, Ali HM, Alshawsh MA, Qadir SW
    J Sci Food Agric, 2012 Jul;92(9):1874-7.
    PMID: 22231455 DOI: 10.1002/jsfa.5554
    Recently much attention has been paid to biologically active plants because of their low production cost and fewer adverse effects compared with chemical drugs. In the present investigation the bioactivity of Phyllanthus niruri ethanol and aqueous extracts was evaluated in vitro.
    Matched MeSH terms: Cell Proliferation/drug effects
  5. Asymmetrical meta-methoxylated diarylpentanoids: Rational design, synthesis and anti-cancer evaluation in-vitro
    Leong SW, Chia SL, Abas F, Yusoff K
    Eur J Med Chem, 2018 Sep 05;157:716-728.
    PMID: 30138803 DOI: 10.1016/j.ejmech.2018.08.039
    In the present study, a series of forty-five asymmetrical meta-methoxylated diarylpentanoids have been synthesized, characterized and evaluated for their in-vitro anti-cancer potential. Among the forty-five analogs, three compounds (20, 33 and 42) have been identified as lead compounds due to their excellent inhibition against five human cancer cell lines including SW620, A549, EJ28, HT1080 and MCF-7. Structure-activity relationship study on cytotoxicity of tested compounds suggested that the presence of meta-oxygenated phenyl ring played a critical role in enhancing their cytotoxic effects. Compounds 33 and 42 in particular, exhibited strongest cytotoxicity against tested cell lines with the IC50 values ranging from 1.1 to 4.3 μM. Subsequent colony formation assay on SW620 cell line showed that both compounds 33 and 42 possessed strong anti-proliferative activity. In addition, flow cytometry based experiments revealed that these compounds could trigger intracellular ROS production thus inducing G2/M-phase cell arrest and apoptosis. All these results suggested that poly meta-oxygenated diarylpentnoid is a promising scaffold which deserved further modification and investigation in the development of natural product-based anti-cancer drug.
    Matched MeSH terms: Cell Proliferation/drug effects
  6. Fulltext Attenuation of Inflammatory Mediators (TNF-α and Nitric Oxide) and Up-Regulation of IL-10 by Wild and Domesticated Basidiocarps of Amauroderma rugosum (Blume & T. Nees) Torrend in LPS-Stimulated RAW264.7 Cells
    Chan PM, Tan YS, Chua KH, Sabaratnam V, Kuppusamy UR
    PLoS One, 2015;10(10):e0139593.
    PMID: 26427053 DOI: 10.1371/journal.pone.0139593
    Amauroderma rugosum, commonly known as "Jiǎzī" in China, is a wild mushroom traditionally used by the Chinese to reduce inflammation, to treat diuretic and upset stomach, and to prevent cancer. It is also used by the indigenous communities in Malaysia to prevent epileptic episodes and incessant crying by babies. The aim of this study was to compare the wild and domesticated basidiocarps of A. rugosum for antioxidant and in vitro anti-inflammatory effects in LPS-stimulated RAW264.7 cells. The wild basidiocarps of A. rugosum were collected from the Belum Forest, Perak, Malaysia and the domesticated basidiocarps of A. rugosum were cultivated in the mushroom house located in the University of Malaya, Kuala Lumpur, Malaysia. Both the wild and domesticated basidiocarps were subjected to ethanolic extraction and the extracts were tested for antioxidant and anti-inflammatory activities. In this study, the crude ethanolic extract of wild (WB) and domesticated (DB) basidiocarps of A. rugosum had comparable total phenolic content and DPPH scavenging activity. However, WB (EC50 = 222.90 μg/mL) displayed a better ABTS cation radical scavenging activity than DB (EC50 = 469.60 μg/mL). Both WB and DB were able to scavenge nitric oxide (NO) radical and suppress the NO production in LPS-stimulated RAW264.7 cells and this effect was mediated through the down-regulation of inducible nitric oxide synthase (iNOS) gene. In addition, both WB and DB caused down-regulation of the inflammatory gene TNF-α and the up-regulation of the anti-inflammatory gene IL-10. There was no inhibitory effect of WB and DB on nuclear translocation of NF-κB p65. In conclusion, the wild and domesticated basidiocarps of A. rugosum possessed antioxidant and in vitro anti-inflammatory properties. WB and DB inhibited downstream inflammatory mediators (TNF-α and NO) and induced anti-inflammatory cytokine IL-10 production. No inhibitory effects shown on upstream nuclear translocation of NF-κB p65. WB and DB exhibited antioxidant activity and attenuation of proinflammatory mediators and therefore, A. rugosum may serve as a potential therapeutic agent in the management of inflammation.
    Matched MeSH terms: Cell Proliferation/drug effects
  7. Fulltext Basic fibroblast growth factor modulates cell cycle of human umbilical cord-derived mesenchymal stem cells
    Ramasamy R, Tong CK, Yip WK, Vellasamy S, Tan BC, Seow HF
    Cell Prolif, 2012 Apr;45(2):132-9.
    PMID: 22309282 DOI: 10.1111/j.1365-2184.2012.00808.x
    BACKGROUND: Mesenchymal stem cells (MSC) have great potential in regenerative medicine, immunotherapy and gene therapy due to their unique properties of self-renewal, high plasticity, immune modulation and ease for genetic modification. However, production of MSC at sufficient clinical scale remains an issue as in vitro generation of MSC inadequately fulfils the demand with respect to patients.

    OBJECTIVES: This study has aimed to establish optimum conditions to generate and characterize MSC from human umbilical cord (UC-MSC).

    MATERIALS AND METHODS: To optimize MSC population growth, basic fibroblast growth factor (bFGF) was utilized in culture media. Effects of bFGF on expansion kinetics, cell cycle, survival of UC-MSC, cytokine secretion, expression of early stem-cell markers and immunomodulation were investigated.

    RESULTS: bFGF supplementation profoundly enhanced UC-MSC proliferation by reducing population doubling time without altering immunophenotype and immunomodulatory function of UC-MSC. However, cell cycle studies revealed that bFGF drove the cells into the cell cycle, as a higher proportion of cells resided in S phase and progressed into M phase. Consistent with this, bFGF was shown to promote expression of cyclin D proteins and their relevant kinases to drive UC-MSC to transverse cell cycle check points, thus, committing the cells to DNA synthesis. Furthermore, supplementation with bFGF changed the cytokine profiles of the cells and reduced their apoptotic level.

    CONCLUSION: Our study showed that bFGF supplementation of UC-MSC culture enhanced the cells' growth kinetics without compromising their nature.

    Matched MeSH terms: Cell Proliferation/drug effects
  8. Fulltext Basic fibroblast growth factor with human serum supplementation: enhancement of human chondrocyte proliferation and promotion of cartilage regeneration
    Chua KH, Aminuddin BS, Fuzina NH, Ruszymah BH
    Singapore Med J, 2007 Apr;48(4):324-32.
    PMID: 17384880
    The objectives of this study were to determine the optimum concentration of basic fibroblast growth factor (bFGF) in foetal bovine serum (FBS) or human serum (HS) supplemented medium for adult human nasal septum chondrocyte culture and to evaluate the potential of cartilage regeneration.
    Matched MeSH terms: Cell Proliferation/drug effects
  9. Fulltext Berberine Inhibits Telomerase Activity and Induces Cell Cycle Arrest and Telomere Erosion in Colorectal Cancer Cell Line, HCT 116
    Samad MA, Saiman MZ, Abdul Majid N, Karsani SA, Yaacob JS
    Molecules, 2021 Jan 13;26(2).
    PMID: 33450878 DOI: 10.3390/molecules26020376
    Colorectal cancer (CRC) is the most common cancer among males and females, which is associated with the increment of telomerase level and activity. Some plant-derived compounds are telomerase inhibitors that have the potential to decrease telomerase activity and/or level in various cancer cell lines. Unfortunately, a deeper understanding of the effects of telomerase inhibitor compound(s) on CRC cells is still lacking. Therefore, in this study, the aspects of telomerase inhibitors on a CRC cell line (HCT 116) were investigated. Screening on HCT 116 at 48 h showed that berberine (10.30 ± 0.89 µg/mL) is the most effective (lowest IC50 value) telomerase inhibitor compared to boldine (37.87 ± 3.12 µg/mL) and silymarin (>200 µg/mL). Further analyses exhibited that berberine treatment caused G0/G1 phase arrest at 48 h due to high cyclin D1 (CCND1) and low cyclin-dependent kinase 4 (CDK4) protein and mRNA levels, simultaneous downregulation of human telomerase reverse transcriptase (TERT) mRNA and human telomerase RNA component (TERC) levels, as well as a decrease in the TERT protein level and telomerase activity. The effect of berberine treatment on the cell cycle was time dependent as it resulted in a delayed cell cycle and doubling time by 2.18-fold. Telomerase activity and level was significantly decreased, and telomere erosion followed suit. In summary, our findings suggested that berberine could decrease telomerase activity and level of HCT 116, which in turn inhibits the proliferative ability of the cells.
    Matched MeSH terms: Cell Proliferation/drug effects
  10. Beyond lipid-lowering: role of statins in endometrial cancer
    Hafizz AMHA, Zin RRM, Aziz NHA, Kampan NC, Shafiee MN
    Mol Biol Rep, 2020 Oct;47(10):8199-8207.
    PMID: 32897522 DOI: 10.1007/s11033-020-05760-5
    As the obesity rates dramatically increased across the globe, the risk of endometrial cancer (EC) has substantially increased. Measures to improve the EC outcome is utmost important, especially data have shown that women at their reproductive age are commonly affected. No doubt, surgical intervention is a standard treatment for EC. However, the fact that this cancer could arise from metabolic diseases, additional therapy by lipid-lowering agent could be utilized to change the tumour environment. We review available evidence to support the use of this agent in the clinical setting. We search available evidence on the use of statin in EC, in various settings including cell lines, animal and human study. The possible actions at different molecular pathways leading to cellular changes and proliferation of cell were evaluated. The venture in drug repositioning of statins as a chemo-preventive potential agent in EC has gained attention in gynaecological oncology practice worldwide. Lipid-lowering effect by statins may exerted a chemoprotective effect in EC, but there is still lack of evidence on statins use to improve prognosis and survival in EC. Through the cholesterol-lowering effect of statins; theoretically, it could inhibit cell growth, proliferation, migration, and lead to apoptosis. Epidemiological studies suggested that statins may improve survival rate among EC patients. However, some evidence revealed the effects were only more prominent in type II EC. Notwithstanding that several studies also showed no benefit of statins in EC. Hence we highlight the limitations of these studies in this review. In line with recent literature on the topic, statins may play a role in EC management. Future studies for a proper systematic review and randomized controlled study are needed to answer some uncertainties of statins effect in EC.
    Matched MeSH terms: Cell Proliferation/drug effects
  11. Fulltext Bioactive Proteins in Channa striata Promote Wound Healing through Angiogenesis and Cell Proliferation
    Kwan SH, Abdul Aziz NHK, Ismail MN
    Protein Pept Lett, 2020;27(1):48-59.
    PMID: 31362651 DOI: 10.2174/0929866526666190730121711
    BACKGROUND: Channa striata are speculated to contain bioactive proteins with the ability to enhancing wound healing. It is commonly consumed after surgery for a faster recovery of the wound.

    OBJECTIVE: To identify the bioactive proteins and evaluate their ability in cell proliferation and angiogenesis promotion.

    MATERIAL AND METHODS: Freeze-Dried Water Extracts (FDWE) and Spray-Dried Water Extracts (SDWE) of C. striata were tested with MTT assay using EA.hy926 endothelial cell line and ex-vivo aortic ring assay. Later the proteins were fractionated and analysed using an LC-QTOF mass spectrometer. The data generated were matched with human gene database for protein similarity and pathway identification.

    RESULTS: Both samples have shown positive cell proliferation and pro-angiogenic activity. Four essential proteins/genes were identified, which are collagen type XI, actin 1, myosin light chain and myosin heavy chain. The pathways discovered that related to these proteins are integrin pathway, Slit-Robo signalling pathway and immune response C-C Chemokine Receptor-3 signalling pathway in eosinophils, which contribute towards wound healing mechanism.

    CONCLUSIONS: The results presented have demonstrated that C. striata FDWE and SDWE protein fractions contain bioactive proteins that are highly similar to human proteins and thus could be involved in the wound healing process via specific biological pathways.

    Matched MeSH terms: Cell Proliferation/drug effects*
  12. Bioactivity-guided isolation of anticancer agents from Bauhinia kockiana Korth
    Chew YL, Lim YY, Stanslas J, Ee GC, Goh JK
    Afr J Tradit Complement Altern Med, 2014;11(3):291-9.
    PMID: 25371595
    BACKGROUND: Flowers of Bauhinia kockiana were investigated for their anticancer properties.

    METHODS: Gallic acid (1), and methyl gallate (2), were isolated via bioassay-directed isolation, and they exhibited anticancer properties towards several cancer cell lines, examined using MTT cell viability assay. Pyrogallol (3) was examined against the same cancer cell lines to deduce the bioactive functional group of the phenolic compounds.

    RESULTS: The results showed that the phenolic compounds could exhibit moderate to weak cytotoxicity towards certain cell lines (GI50 30 - 86 µM), but were inactive towards DU145 prostate cancer cell (GI50 > 100 µM).

    CONCLUSION: It was observed that pyrogallol moiety was one of the essential functional structures of the phenolic compounds in exhibiting anticancer activity. Also, the carboxyl group of compound 1 was also important in anticancer activity. Examination of the PC-3 cells treated with compound 1 using fluorescence microscopy showed that PC-3 cells were killed by apoptosis.

    Matched MeSH terms: Cell Proliferation/drug effects
  13. Fulltext Biomedical properties of a natural dietary plant metabolite, zerumbone, in cancer therapy and chemoprevention trials
    Rahman HS, Rasedee A, Yeap SK, Othman HH, Chartrand MS, Namvar F, et al.
    Biomed Res Int, 2014;2014:920742.
    PMID: 25025076 DOI: 10.1155/2014/920742
    Zerumbone (ZER) is a naturally occurring dietary compound, present in many natural foods consumed today. The compound derived from several plant species of the Zingiberaceae family that has been found to possess multiple biomedical properties, such as antiproliferative, antioxidant, anti-inflammatory, and anticancer activities. However, evidence of efficacy is sparse, pointing to the need for a more systematic review for assessing scientific evidence to support therapeutic claims made for ZER and to identify future research needs. This review provides an updated overview of in vitro and in vivo investigations of ZER, its cancer chemopreventive properties, and mechanisms of action. Therapeutic effects of ZER were found to be scientifically plausible and could be explained partially by in vivo and in vitro pharmacological activities. Much of the research outlined in this paper will serve as a foundation to explain ZER anticancer bioactivity, which will open the door for the development of strategies in the treatment of malignancies using ZER.
    Matched MeSH terms: Cell Proliferation/drug effects*
  14. Fulltext Biosafety evaluation of culture-expanded human chondrocytes with growth factor cocktail: a preclinical study
    Al-Masawa ME, Wan Kamarul Zaman WS, Chua KH
    Sci Rep, 2020 12 09;10(1):21583.
    PMID: 33299022 DOI: 10.1038/s41598-020-78395-y
    The scarcity of chondrocytes is a major challenge for cartilage tissue engineering. Monolayer expansion is necessary to amplify the limited number of chondrocytes needed for clinical application. Growth factors are often added to improve monolayer culture conditions, promoting proliferation, and enhancing chondrogenesis. Limited knowledge on the biosafety of the cell products manipulated with growth factors in culture has driven this study to evaluate the impact of growth factor cocktail supplements in chondrocyte culture medium on chondrocyte genetic stability and tumorigenicity. The growth factors were basic fibroblast growth factor (b-FGF), transforming growth factor β2 (TGF β2), insulin-like growth factor 1 (IGF-1), insulin-transferrin-selenium (ITS), and platelet-derived growth factor (PD-GF). Nasal septal chondrocytes cultured in growth factor cocktail exhibited a significantly high proliferative capacity. Comet assay revealed no significant DNA damage. Flow cytometry showed chondrocytes were mostly at G0-G1 phase, exhibiting normal cell cycle profile with no aneuploidy. We observed a decreased tumour suppressor genes' expression (p53, p21, pRB) and no TP53 mutations or tumour formation after 6 months of implantation in nude mice. Our data suggest growth factor cocktail has a low risk of inducing genotoxic and tumorigenic effects on chondrocytes up to passage 6 with 16.6 population doublings. This preclinical tumorigenicity and genetic instability evaluation is crucial for further clinical works.
    Matched MeSH terms: Cell Proliferation/drug effects*
  15. Biosorption of copper and zinc by immobilised and free algal biomass, and the effects of metal biosorption on the growth and cellular structure of Chlorella sp. and Chlamydomonas sp. isolated from rivers in Penang, Malaysia
    Maznah WO, Al-Fawwaz AT, Surif M
    J Environ Sci (China), 2012;24(8):1386-93.
    PMID: 23513679
    In this study, the biosorption of copper and zinc ions by Chlorella sp. and Chlamydomonas sp. isolated from local environments in Malaysia was investigated in a batch system and by microscopic analyses. Under optimal biosorption conditions, the biosorption capacity of Chlorella sp. for copper and zinc ions was 33.4 and 28.5 mg/g, respectively, after 6 hr of biosorption in an immobilised system. Batch experiments showed that the biosorption capacity of algal biomass immobilised in the form of sodium alginate beads was higher than that of the free biomass. Scanning electron microscopy and energy-dispersive X-ray spectroscopy analyses revealed that copper and zinc were mainly sorbed at the cell surface during biosorption. Exposure to 5 mg/L of copper and zinc affected both the chlorophyll content and cell count of the algal cells after the first 12 hr of contact time.
    Matched MeSH terms: Cell Proliferation/drug effects
  16. Bisphenol A exposure disturbs the bone metabolism: An evolving interest towards an old culprit
    Thent ZC, Froemming GRA, Muid S
    Life Sci, 2018 Apr 01;198:1-7.
    PMID: 29432759 DOI: 10.1016/j.lfs.2018.02.013
    Bisphenol A (BPA) (2,2,-bis (hydroxyphenyl) propane), a well-known endocrine disruptor (ED), is the exogenous chemical that mimic the natural endogenous hormone like oestrogen. Due to its extensive exposure to humans, BPA is considered to be a major toxicological agent for general population. Environmental exposure of BPA results in adverse health outcomes including bone loss. BPA disturbs the bone health by decreasing the plasma calcium level and inhibiting the calcitonin secretion. BPA also stimulated differentiation and induced apoptosis in human osteoblasts and osteoclasts. However, little is known about the underlying mechanisms of the untoward effect of BPA against bone metabolism. The present review gives an overview on the possible mechanisms of BPA towards bone loss. The previous literature shows that BPA exerts its toxic effect on bone cells by binding to the oestrogen related receptor-gamma (ERγ), reducing the bone morphogenic protein-2 (BMP-2) and alkaline phosphatase (ALP) activities. BPA interrupts the bone metabolism via RANKL, apoptosis and Wnt/β-catenin signaling pathways. It is, however, still debated on the exact underlying mechanism of BPA against bone health. We summarised the molecular evidences with possible mechanisms of BPA, an old environmental culprit, in bone loss and enlightened the underlying understanding of adverse action of BPA in the society.
    Matched MeSH terms: Cell Proliferation/drug effects
  17. Bone marrow-derived mesenchymal stem cells modulate BV2 microglia responses to lipopolysaccharide
    Ooi YY, Ramasamy R, Rahmat Z, Subramaiam H, Tan SW, Abdullah M, et al.
    Int Immunopharmacol, 2010 Dec;10(12):1532-40.
    PMID: 20850581 DOI: 10.1016/j.intimp.2010.09.001
    The immunoregulatory properties of mesenchymal stem cells (MSC) have been demonstrated on a wide range of cells. Here, we describe the modulatory effects of mouse bone marrow-derived MSC on BV2 microglia proliferation rate, nitric oxide (NO) production and CD40 expression. Mouse bone marrow MSC were co-cultured with BV2 cells at various seeding density ratios and activated with lipopolysaccharide (LPS). We show that MSC exert an anti-proliferative effect on microglia and are potent producers of NO when stimulated by soluble factors released by LPS-activated BV2. MSC suppressed proliferation of both untreated and LPS-treated microglia in a dose-dependent manner, significantly reducing BV2 proliferation at seeding density ratios of 1:0.2 and 1:0.1 (pcells at different ratios revealed interesting dynamics in NO production. A high number of MSC significantly increases NO in co-cultures whilst a lower number reduces NO. The increased NO levels in co-cultures may be MSC-derived, as we also show that activated BV2 cells stimulate MSC to produce NO. Cell-cell interaction is not a requirement for this effect as soluble factors released by activated BV2 cells alone do stimulate MSC to produce high levels of NO. Although NO is implicated as a mediator for T cell proliferation, it does not appear to play a major role in the suppression of microglia proliferation. Additionally, MSC reduced the expression of the microglial co-stimulator molecule, CD40. Collectively, these regulatory effects of MSC on microglia offer insight into the potential moderating properties of MSC on inflammatory responses within the CNS.
    Matched MeSH terms: Cell Proliferation/drug effects
  18. Bone regeneration performance of surface-treated porous titanium
    Amin Yavari S, van der Stok J, Chai YC, Wauthle R, Tahmasebi Birgani Z, Habibovic P, et al.
    Biomaterials, 2014 Aug;35(24):6172-81.
    PMID: 24811260 DOI: 10.1016/j.biomaterials.2014.04.054
    The large surface area of highly porous titanium structures produced by additive manufacturing can be modified using biofunctionalizing surface treatments to improve the bone regeneration performance of these otherwise bioinert biomaterials. In this longitudinal study, we applied and compared three types of biofunctionalizing surface treatments, namely acid-alkali (AcAl), alkali-acid-heat treatment (AlAcH), and anodizing-heat treatment (AnH). The effects of treatments on apatite forming ability, cell attachment, cell proliferation, osteogenic gene expression, bone regeneration, biomechanical stability, and bone-biomaterial contact were evaluated using apatite forming ability test, cell culture assays, and animal experiments. It was found that AcAl and AnH work through completely different routes. While AcAl improved the apatite forming ability of as-manufactured (AsM) specimens, it did not have any positive effect on cell attachment, cell proliferation, and osteogenic gene expression. In contrast, AnH did not improve the apatite forming ability of AsM specimens but showed significantly better cell attachment, cell proliferation, and expression of osteogenic markers. The performance of AlAcH in terms of apatite forming ability and cell response was in between both extremes of AnH and AsM. AcAl resulted in significantly larger volumes of newly formed bone within the pores of the scaffold as compared to AnH. Interestingly, larger volumes of regenerated bone did not translate into improved biomechanical stability as AnH exhibited significantly better biomechanical stability as compared to AcAl suggesting that the beneficial effects of cell-nanotopography modulations somehow surpassed the benefits of improved apatite forming ability. In conclusion, the applied surface treatments have considerable effects on apatite forming ability, cell attachment, cell proliferation, and bone ingrowth of the studied biomaterials. The relationship between these properties and the bone-implant biomechanics is, however, not trivial.
    Matched MeSH terms: Cell Proliferation/drug effects
  19. Cancer chemopreventive activity of maslinic acid: suppression of COX-2 expression and inhibition of NF-κB and AP-1 activation in Raji cells
    Hsum YW, Yew WT, Hong PL, Soo KK, Hoon LS, Chieng YC, et al.
    Planta Med, 2011 Jan;77(2):152-7.
    PMID: 20669087 DOI: 10.1055/s-0030-1250203
    Chronic inflammation is one of the predisposing factors for neoplastic transformation. Targeting inflammation through suppression of the pro-inflammatory pathway by dietary phytochemicals provides an important strategy for cancer prevention. Maslinic acid is a novel natural triterpenoid known to inhibit proliferation and induce apoptosis in some tumor cell lines. Although maslinic acid has cytotoxic and pro-apoptotic effects on cancer cells, the underlying mechanisms of its effects on the inflammatory pathway have yet to be elucidated. It has been reported that abnormal expression of pro-inflammatory enzyme cyclooxygenase-2 (COX-2) causes promotion of cellular proliferation, suppression of apoptosis, enhancement of angiogenesis and invasiveness. In the present study, the suppressive effect of maslinic acid on COX-2 expression and the binding activity of upstream transcription factors NF- κB and AP-1, which are known to regulate COX-2 transcriptional activation, were assessed using Raji cells. The anti-inflammatory action of maslinic acid was benchmarked against oleanolic acid and other standard drugs. Western blot analysis and electrophoretic mobility shift assay (EMSA) were employed to analyze COX-2 expression as well as NF- κB and AP-1 binding activity. Our results showed that maslinic acid suppresses COX-2 expression in a concentration-dependent manner. Likewise, the constitutive nuclear NF- κB (p65) activity as well as phorbol 12-myristate 13-acetate (PMA)- and sodium N-butyrate (SnB)-induced AP-1 binding activity in Raji cells were significantly reduced following treatment with maslinic acid. Since maslinic acid suppresses COX-2 expression in Raji cells at concentrations that also lowered the NF- κB (p65) and AP-1 binding activity, it is possible that the suppression of COX-2 by this natural triterpenoid might be achieved, at least in part, via the NF- κB and AP-1 signaling pathways.
    Matched MeSH terms: Cell Proliferation/drug effects
  20. Fulltext Cancer-associated fibroblasts promote proliferation of endometrial cancer cells
    Subramaniam KS, Tham ST, Mohamed Z, Woo YL, Mat Adenan NA, Chung I
    PLoS One, 2013;8(7):e68923.
    PMID: 23922669 DOI: 10.1371/journal.pone.0068923
    Endometrial cancer is the most commonly diagnosed gynecologic malignancy worldwide; yet the tumor microenvironment, especially the fibroblast cells surrounding the cancer cells, is poorly understood. We established four primary cultures of fibroblasts from human endometrial cancer tissues (cancer-associated fibroblasts, CAFs) using antibody-conjugated magnetic bead isolation. These relatively homogenous fibroblast cultures expressed fibroblast markers (CD90, vimentin and alpha-smooth muscle actin) and hormonal (estrogen and progesterone) receptors. Conditioned media collected from CAFs induced a dose-dependent proliferation of both primary cultures and cell lines of endometrial cancer in vitro (175%) when compared to non-treated cells, in contrast to those from normal endometrial fibroblast cell line (51%) (P<0.0001). These effects were not observed in fibroblast culture derived from benign endometrial hyperplasia tissues, indicating the specificity of CAFs in affecting endometrial cancer cell proliferation. To determine the mechanism underlying the differential fibroblast effects, we compared the activation of PI3K/Akt and MAPK/Erk pathways in endometrial cancer cells following treatment with normal fibroblasts- and CAFs-conditioned media. Western blot analysis showed that the expression of both phosphorylated forms of Akt and Erk were significantly down-regulated in normal fibroblasts-treated cells, but were up-regulated/maintained in CAFs-treated cells. Treatment with specific inhibitors LY294002 and U0126 reversed the CAFs-mediated cell proliferation (P<0.0001), suggesting for a role of these pathways in modulating endometrial cancer cell proliferation. Rapamycin, which targets a downstream molecule in PI3K pathway (mTOR), also suppressed CAFs-induced cell proliferation by inducing apoptosis. Cytokine profiling analysis revealed that CAFs secrete higher levels of macrophage chemoattractant protein (MCP)-1, interleukin (IL)-6, IL-8, RANTES and vascular endothelial growth factor (VEGF) than normal fibroblasts. Our data suggests that in contrast to normal fibroblasts, CAFs may exhibit a pro-tumorigenic effect in the progression of endometrial cancer, and PI3K/Akt and MAPK/Erk signaling may represent critical regulators in how endometrial cancer cells respond to their microenvironment.
    Matched MeSH terms: Cell Proliferation/drug effects
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