Displaying publications 141 - 160 of 543 in total

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  1. Fulltext Perturbation of cellular immune functions in cigarette smokers and protection by palm oil vitamin E supplementation
    Jubri Z, Latif AA, Top AG, Ngah WZ
    Nutr J, 2013;12:2.
    PMID: 23286246 DOI: 10.1186/1475-2891-12-2
    BACKGROUND:
    Cigarette smoke contains free radicals and an have adverse effect to the immune system. Supplementation of palm oil vitamin E (palmvitee), is known has antioxidant properties is thought to be beneficial for system immune protection against free radicals activity. The objective of the study was to determine the effect of palmvitee supplementation on immune response in smokers.

    METHODS:
    This study involved a group of smokers and nonsmokers who received 200 mg/day palmvitee and placebo for the control group. Blood samples were taken at 0, 12 and 24 weeks of supplementation. Plasma tocopherol and tocotrienol were determined by HPLC, lymphocyte proliferation by lymphocyte transformation test (LTT) and enumeration of lymphocytes T and B cells by flow cytometry. Statistical analysis was performed by Mann-Whitney U-test for non-parametric data distribution and correlation among the variables was examined by Spearman.

    RESULTS:
    Plasma tocopherol and tocotrienol were increased in vitamin E supplemented group as compared to placebo group. Urine cotinine levels and serum α1-antitrypsin were significantly higher in smokers compared to nonsmokers. Lymphocyte proliferation induced by PHA showed an increasing trend with palmvitee supplementation in both smokers and nonsmokers. Natural killer cells were decreased; CD4+ cells and B cells were increased in smokers compared to nonsmokers but were unaffected with vitamin E supplementation except in the percentage of B cells which were increased in nonsmokers supplemented palmvitee compared to placebo. CD4+/CD8+ ratio was increased in smokers compared to nonsmokers. The high TWBC count observed in smokers correlated with the increased CD4+ and B cells.

    CONCLUSIONS:
    Smoking caused alterations in certain immune parameters and palmvitee supplementation tended to cause an increase in lymphocytes transformation test but had no effect on CD3+, CD4+, CD8+, NK cells and B cells except B cells percentage in nonsmokers.
    Matched MeSH terms: Cell Proliferation/drug effects
  2. Fulltext In vivo evaluation of ethanolic extract of Zingiber officinale rhizomes for its protective effect against liver cirrhosis
    Abdulaziz Bardi D, Halabi MF, Abdullah NA, Rouhollahi E, Hajrezaie M, Abdulla MA
    Biomed Res Int, 2013;2013:918460.
    PMID: 24396831 DOI: 10.1155/2013/918460
    Zingiber officinale is a traditional medicine against various disorders including liver diseases.The aim of this study was to assess the hepatoprotective activity of the ethanolic extract of rhizomes of Z. officinale (ERZO) against thioacetamide-induced hepatotoxicity in rats. Five groups of male Sprague Dawley have been used. In group 1 rats received intraperitoneal (i.p.) injection of normal saline while groups 2-5 received thioacetamide (TAA, 200 mg/kg; i.p.) for induction of liver cirrhosis, thrice weekly for eight weeks. Group 3 received 50 mg/kg of silymarin. The rats in groups 4 and 5 received 250 and 500 mg/kg of ERZO (dissolved in 10% Tween), respectively. Hepatic damage was assessed grossly and microscopically for all of the groups. Results confirmed the induction of liver cirrhosis in group 2 whilst administration of silymarin or ERZO significantly reduced the impact of thioacetamide toxicity. These groups decreased fibrosis of the liver tissues. Immunohistochemistry assessment against proliferating cell nuclear antigen did not show remarkable proliferation in the ERZO-treated rats when compared with group 2. Moreover, factions of the ERZO extract were tested on Hep-G2 cells and showed antiproliferative activity (IC50 38-60 μ g/mL). This study showed hepatoprotective effect of ERZO.
    Matched MeSH terms: Cell Proliferation/drug effects
  3. Fulltext Antioxidant, antiproliferative, and antiangiogenesis effects of polyphenol-rich seaweed (Sargassum muticum)
    Namvar F, Mohamad R, Baharara J, Zafar-Balanejad S, Fargahi F, Rahman HS
    Biomed Res Int, 2013;2013:604787.
    PMID: 24078922 DOI: 10.1155/2013/604787
    In the present study, we evaluated the effect of brown seaweeds Sargassum muticum methanolic extract (SMME), against MCF-7 and MDA-MB-231 breast cancer cell lines proliferation. This algae extract was also evaluated for reducing activity and total polyphenol content. The MTT assay results indicated that the extracts were cytotoxic against breast cancer cell lines in a dose-dependent manner, with IC50 of 22 μg/ml for MCF-7 and 55 μg/ml for MDA-MB-231 cell lines. The percentages of apoptotic MCF-7-treated cells increased from 13% to 67% by increasing the concentration of the SMME. The antiproliferative efficacy of this algal extract was positively correlated with the total polyphenol contents, suggesting a causal link related to extract content of phenolic acids. Cell cycle analysis showed a significant increase in the accumulation of SMME-treated cells at sub-G1 phase, indicating the induction of apoptosis by SMME. Further apoptosis induction was confirmed by Hoechst 33342 and AO/PI staining. Also SMME implanted in vivo into fertilized chicken eggs induced dose-related antiangiogenic activity in the chorioallantoic membrane (CAM). Our results imply a new insight on the novel function of Sargassum muticum polyphenol-rich seaweed in cancer research by induction of apoptosis, antioxidant, and antiangiogenesis effects.
    Matched MeSH terms: Cell Proliferation/drug effects
  4. Fulltext In vitro wound healing potential and identification of bioactive compounds from Moringa oleifera Lam
    Muhammad AA, Pauzi NA, Arulselvan P, Abas F, Fakurazi S
    Biomed Res Int, 2013;2013:974580.
    PMID: 24490175 DOI: 10.1155/2013/974580
    Moringa oleifera Lam. (M. oleifera) from the monogeneric family Moringaceae is found in tropical and subtropical countries. The present study was aimed at exploring the in vitro wound healing potential of M. oleifera and identification of active compounds that may be responsible for its wound healing action. The study included cell viability, proliferation, and wound scratch test assays. Different solvent crude extracts were screened, and the most active crude extract was further subjected to differential bioguided fractionation. Fractions were also screened and most active aqueous fraction was finally obtained for further investigation. HPLC and LC-MS/MS analysis were used for identification and confirmation of bioactive compounds. The results of our study demonstrated that aqueous fraction of M. oleifera significantly enhanced proliferation and viability as well as migration of human dermal fibroblast (HDF) cells compared to the untreated control and other fractions. The HPLC and LC-MS/MS studies revealed kaempferol and quercetin compounds in the crude methanolic extract and a major bioactive compound Vicenin-2 was identified in the bioactive aqueous fraction which was confirmed with standard Vicenin-2 using HPLC and UV spectroscopic methods. These findings suggest that bioactive fraction of M. oleifera containing Vicenin-2 compound may enhance faster wound healing in vitro.
    Matched MeSH terms: Cell Proliferation/drug effects
  5. Cytokinetic study of MCF-7 cells treated with commercial and recombinant bromelain
    Fouz N, Amid A, Hashim YZ
    Asian Pac J Cancer Prev, 2014 Jan;14(11):6709-14.
    PMID: 24377593
    BACKGROUND: Breast cancer is a leading cause of death in women. The available chemotherapy drugs have been associated with many side effects. Bromelain has novel medicinal qualities including anti-inflammatory, anti-thrombotic, fibrinolytic and anti-cancer functions. Commercially available bromelain is obtained through tedious methods; therefore, recombinant bromelain may provide a cheaper and simpler choice with similar quality.

    MATERIALS AND METHODS: This study aimed to assess the effects of commercial and recombinant bromelain on the cytokinetic behavior of MCF-7 breast cancer cells and their potential as therapeutic alternatives in cancer treatment. Cytotoxic activities of commercial and recombinant bromelain were determined using (sulforhodamine) SRB assay. Next, cell viability assays were conducted to determine effects of commercial and recombinant bromelain on MCF-7 cell cytokinetic behavior. Finally, the established growth kinetic data were used to modify a model that predicts the effects of commercial and recombinant bromelain on MCF-7 cells.

    RESULTS: Commercial and recombinant bromelain exerted strong effects towards decreasing the cell viability of MCF-7 cells with IC50 values of 5.13 μg/mL and 6.25 μg/mL, respectively, compared to taxol with an IC50 value of 0.063 μg/mL. The present results indicate that commercial and recombinant bromelain both have anti-proliferative activity, reduced the number of cell generations from 3.92 to 2.81 for commercial bromelain and to 2.86 for recombinant bromelain, while with taxol reduction was to 3.12. Microscopic observation of bromelain-treated MCF-7 cells demonstrated detachment. Inhibition activity was verified with growth rates decreased dynamically from 0.009 h-1 to 0.0059 h-1 for commercial bromelain and to 0.0063 h-1 for recombinant bromelain.

    CONCLUSIONS: Commercial and recombinant bromelain both affect cytokinetics of MCF-7 cells by decreasing cell viability, demonstrating similar strength to taxol.

    Matched MeSH terms: Cell Proliferation/drug effects*
  6. Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities
    Yoon YK, Ali MA, Wei AC, Choon TS, Osman H, Parang K, et al.
    Bioorg Med Chem, 2014 Jan 15;22(2):703-10.
    PMID: 24387981 DOI: 10.1016/j.bmc.2013.12.029
    A total of 15 novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. All compounds showed better inhibition on SIRT2 as compared to SIRT1. Among these, compound 5j displayed the best inhibitory activity for SIRT1 (IC50=58.43μM) as well as for SIRT2 (IC50=45.12μM). Cell cytotoxicity assays also showed that compound 5j possesses good antitumor activity against two different cancer cell lines derived from breast cancer (MCF-7 and MDA-MB-468). A simple structure-activity-relationship (SAR) study of the newly synthesized benzimidazole derivatives was also discussed.
    Matched MeSH terms: Cell Proliferation/drug effects
  7. Macroline, akuammiline, sarpagine, and ajmaline alkaloids from Alstonia macrophylla
    Lim SH, Low YY, Sinniah SK, Yong KT, Sim KS, Kam TS
    Phytochemistry, 2014 Feb;98:204-15.
    PMID: 24342109 DOI: 10.1016/j.phytochem.2013.11.014
    A total of seventeen alkaloids, comprising six macroline (including alstofolinine A, a macroline indole incorporating a butyrolactone ring-E), two ajmaline, one sarpagine, and eight akuammiline alkaloids, were isolated from the stem-bark and leaf extracts of the Malayan Alstonia macrophylla. The structure and relative configurations of these alkaloids were established using NMR, MS and in several instances, confirmed by X-ray diffraction analysis. Six of these alkaloids were effective in reversing multidrug-resistance (MDR) in vincristine-resistant KB cells.
    Matched MeSH terms: Cell Proliferation/drug effects
  8. Fulltext Ethyl-p-methoxycinnamate isolated from Kaempferia galanga inhibits inflammation by suppressing interleukin-1, tumor necrosis factor-α, and angiogenesis by blocking endothelial functions
    Umar MI, Asmawi MZ, Sadikun A, Majid AM, Al-Suede FS, Hassan LE, et al.
    Clinics (Sao Paulo), 2014 Feb;69(2):134-44.
    PMID: 24519205 DOI: 10.6061/clinics/2014(02)10
    The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga.
    Matched MeSH terms: Cell Proliferation/drug effects
  9. AMP-activated protein kinase mediates insulin-like and lipo-mobilising effects of β-glucan-rich polysaccharides isolated from Pleurotus sajor-caju (Fr.), Singer mushroom, in 3T3-L1 cells
    Kanagasabapathy G, Chua KH, Malek SN, Vikineswary S, Kuppusamy UR
    Food Chem, 2014 Feb 15;145:198-204.
    PMID: 24128468 DOI: 10.1016/j.foodchem.2013.08.051
    Mushrooms have been used to treat various diseases for thousands of years. In the present study, the effects of Pleurotus sajor-caju mushroom on lipogenesis, lipolysis and oxidative stress in 3T3-L1 cells were investigated. The β-glucan-rich polysaccharides (GE) from P. sajor-caju stimulated lipogenesis and lipolysis but attenuated protein carbonyl and lipid hydroperoxide levels in 3T3-L1 cells. This extract caused an increase in the expression of 5'-AMP-activated protein kinase subunit γ-2 (PKRAG2) and 5'-AMP-activated protein kinase subunit γ-3 (PKRAG3) when compared to control (untreated) cells. Moreover, GE induced the expressions of hormone-sensitive lipase, adipose triglyceride lipase enzymes, leptin, adiponectin and glucose transporter-4 in 3T3-L1 cells which may have contributed to the lipolytic and insulin-like activities observed in this study. These findings suggest that GE is a novel AMPK activator that may be valuable in the formulation of nutraceuticals and functional food for the prevention and treatment of diabetes mellitus.
    Matched MeSH terms: Cell Proliferation/drug effects
  10. Comparison of the effects between animal-derived trypsin and recombinant trypsin on human skin cells proliferation, gene and protein expression
    Manira M, Khairul Anuar K, Seet WT, Ahmad Irfan AW, Ng MH, Chua KH, et al.
    Cell Tissue Bank, 2014 Mar;15(1):41-9.
    PMID: 23456438 DOI: 10.1007/s10561-013-9368-y
    Animal-derivative free reagents are preferred in skin cell culture for clinical applications. The aim of this study was to compare the performance and effects between animal-derived trypsin and recombinant trypsin for skin cells culture and expansion. Full thickness human skin was digested in 0.6 % collagenase for 6 h to liberate the fibroblasts, followed by treatment with either animal-derived trypsin; Trypsin EDTA (TE) or recombinant trypsin; TrypLE Select (TS) to liberate the keratinocytes. Both keratinocytes and fibroblasts were then culture-expanded until passage 2. Trypsinization for both cell types during culture-expansion was performed using either TE or TS. Total cells yield was determined using a haemocytometer. Expression of collagen type I, collagen type III (Col-III), cytokeratin 10, and cytokeratin 14 genes were quantified via RT-PCR and further confirmed with immunocytochemical staining. The results of our study showed that the total cell yield for both keratinocytes and fibroblasts treated with TE or TS were comparable. RT-PCR showed that expression of skin-specific genes except Col-III was higher in the TS treated group compared to that in the TE group. Expression of proteins specific to the two cell types were confirmed by immunocytochemical staining in both TE and TS groups. In conclusion, the performance of the recombinant trypsin is comparable with the well-established animal-derived trypsin for human skin cell culture expansion in terms of cell yield and expression of specific cellular markers.
    Matched MeSH terms: Cell Proliferation/drug effects
  11. Cellular uptake and anticancer effects of mucoadhesive curcumin-containing chitosan nanoparticles
    Chuah LH, Roberts CJ, Billa N, Abdullah S, Rosli R
    Colloids Surf B Biointerfaces, 2014 Apr 1;116:228-36.
    PMID: 24486834 DOI: 10.1016/j.colsurfb.2014.01.007
    Curcumin, which is derived from turmeric has gained much attention in recent years for its anticancer activities against various cancers. However, due to its poor absorption, rapid metabolism and elimination, curcumin has a very low oral bioavailability. Therefore, we have formulated mucoadhesive nanoparticles to deliver curcumin to the colon, such that prolonged contact between the nanoparticles and the colon leads to a sustained level of curcumin in the colon, improving the anticancer effect of curcumin on colorectal cancer. The current work entails the ex vivo mucoadhesion study of the formulated nanoparticles and the in vitro effect of mucoadhesive interaction between the nanoparticles and colorectal cancer cells. The ex vivo study showed that curcumin-containing chitosan nanoparticles (CUR-CS-NP) have improved mucoadhesion compared to unloaded chitosan nanoparticles (CS-NP), suggesting that curcumin partly contributes to the mucoadhesion process. This may lead to an enhanced anticancer effect of curcumin when formulated in CUR-CS-NP. Our results show that CUR-CS-NP are taken up to a greater extent by colorectal cancer cells, compared to free curcumin. The prolonged contact offered by the mucoadhesion of CUR-CS-NP onto the cells resulted in a greater reduction in percentage cell viability as well as a lower IC50, indicating a potential improved treatment outcome. The formulation and free curcumin appeared to induce cell apoptosis in colorectal cancer cells, by arresting the cell cycle at G2/M phase. The superior anticancer effects exerted by CUR-CS-NP indicated that this could be a potential treatment for colorectal cancer.
    Matched MeSH terms: Cell Proliferation/drug effects
  12. RK-1355A and B, novel quinomycin derivatives isolated from a microbial metabolites fraction library based on NPPlot screening
    Lim CL, Nogawa T, Uramoto M, Okano A, Hongo Y, Nakamura T, et al.
    J Antibiot (Tokyo), 2014 Apr;67(4):323-9.
    PMID: 24496142 DOI: 10.1038/ja.2013.144
    Two novel quinomycin derivatives, RK-1355A (1) and B (2), and one known quinomycin derivative, UK-63,598 (3), were isolated from a microbial metabolites fraction library of Streptomyces sp. RK88-1355 based on Natural Products Plot screening. The structural elucidation of 1 and 2 was established through two-dimensional NMR and mass spectrometric measurements. They belong to a class of quinomycin antibiotics family having 3-hydroxyquinaldic acid and a sulfoxide moiety. They are the first examples for natural products as a quinoline type quinomycin having a sulfoxide on the intramolecular cross-linkage. They showed potent antiproliferative activities against various cancer cell lines and they were also found to exhibit moderate antibacterial activity.
    Matched MeSH terms: Cell Proliferation/drug effects
  13. Fulltext Antiproliferative activity of king cobra (Ophiophagus hannah) venom L-amino acid oxidase
    Li Lee M, Chung I, Yee Fung S, Kanthimathi MS, Hong Tan N
    Basic Clin Pharmacol Toxicol, 2014 Apr;114(4):336-43.
    PMID: 24118879 DOI: 10.1111/bcpt.12155
    King cobra (Ophiophagus hannah) venom L-amino acid oxidase (LAAO), a heat-stable enzyme, is an extremely potent antiproliferative agent against cancer cells when compared with LAAO isolated from other snake venoms. King cobra venom LAAO was shown to exhibit very strong antiproliferative activities against MCF-7 (human breast adenocarcinoma) and A549 (human lung adenocarcinoma) cells, with an IC50 value of 0.04±0.00 and 0.05±0.00 μg/mL, respectively, after 72-hr treatment. In comparison, its cytotoxicity was about 3-4 times lower when tested against human non-tumourigenic breast (184B5) and lung (NL 20) cells, suggesting selective antitumour activity. Furthermore, its potency in MCF-7 and A549 cell lines was greater than the effects of doxorubicin, a clinically established cancer chemotherapeutic agent, which showed an IC50 value of 0.18±0.03 and 0.63±0.21 μg/mL, respectively, against the two cell lines. The selective cytotoxic action of the LAAO was confirmed by phycoerythrin (PE) annexin V/7-amino-actinomycin (AAD) apoptotic assay, in which a significant increase in apoptotic cells was observed in LAAO-treated tumour cells than in their non-tumourigenic counterparts. The ability of LAAO to induce apoptosis in tumour cells was further demonstrated using caspase-3/7 and DNA fragmentation assays. We also determined that this enzyme may target oxidative stress in its killing of tumour cells, as its cytotoxicity was significantly reduced in the presence of catalase (a H2O2 scavenger). In view of its heat stability and selective and potent cytotoxic action on cancer cells, king cobra venom LAAO can be potentially developed for treating solid tumours.
    Matched MeSH terms: Cell Proliferation/drug effects*
  14. Trigonelline attenuates the adipocyte differentiation and lipid accumulation in 3T3-L1 cells
    Ilavenil S, Arasu MV, Lee JC, Kim DH, Roh SG, Park HS, et al.
    Phytomedicine, 2014 Apr 15;21(5):758-65.
    PMID: 24369814 DOI: 10.1016/j.phymed.2013.11.007
    Trigonelline is a natural alkaloid mainly found in Trigonella Foenum Graecum (fenugreek) Fabaceae and other edible plants with a variety of medicinal applications. Therefore, we investigated the molecular mechanism of trigonelline (TG) on the inhibition of adipocyte differentiation and lipid accumulation in 3T3-L1 cells. Trigonelline suppressed lipid droplet accumulation in a concentration (75 and 100 μM) dependent manner. Treatment of adipocyte with of TG down regulates the peroxisome proliferator-activated receptor (PPARγ) and CCAAT element binding protein (C/EBP-α) mRNA expression, which leads to further down regulation of other gene such as adiponectin, adipogenin, leptin, resistin and adipocyte fatty acid binding protein (aP2) as compared with respective control cells on 5th and 10th day of differentiation. Further, addition of triognelline along with troglitazone to the adipocyte attenuated the troglitazone effects on PPARγ mediated differentiation and lipid accumulation in 3T3-L1 cells. Trigonelline might compete against troglitazone for its binding to the PPARγ. In addition, adipocyte treated with trigonelline and isoproterenol separately. Isoproterenol, a lipolytic agent which inhibits the fatty acid synthase and GLUT-4 transporter expression via cAMP mediated pathway, we found that similar magnitude response of fatty acid synthase and GLUT-4 transporter expression in trigonelline treated adipocyte. These results suggest that the trigonelline inhibits the adipogenesis by its influences on the expression PPARγ, which leads to subsequent down regulation of PPAR-γ mediated pathway during adipogenesis. Our findings provide key approach to the mechanism underlying the anti-adipogenic activity of trigonelline.
    Matched MeSH terms: Cell Proliferation/drug effects
  15. Chalcones with electron-withdrawing and electron-donating substituents: anticancer activity against TRAIL resistant cancer cells, structure-activity relationship analysis and regulation of apoptotic proteins
    Mai CW, Yaeghoobi M, Abd-Rahman N, Kang YB, Pichika MR
    Eur J Med Chem, 2014 Apr 22;77:378-87.
    PMID: 24675137 DOI: 10.1016/j.ejmech.2014.03.002
    In the present study, a series of 46 chalcones were synthesised and evaluated for antiproliferative activities against the human TRAIL-resistant breast (MCF-7, MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29), nasopharyngeal (CNE-1), erythromyeloblastoid (K-562) and T-lymphoblastoid (CEM-SS) cancer cells. The chalcone 38 containing an amino (-NH2) group on ring A was the most potent and selective against cancer cells. The effects of the chalcone 38 on regulation of 43 apoptosis-related markers in HT-29 cells were determined. The results showed that 20 apoptotic markers (Bad, Bax, Bcl-2, Bcl-w, Bid, Bim, CD40, Fas, HSP27, IGF-1, IGFBP-4, IGFBP-5, Livin, p21, Survivin, sTNF-R2, TRAIL-R2, XIAP, caspase-3 and caspase-8) were either up regulated or down regulated.
    Matched MeSH terms: Cell Proliferation/drug effects
  16. Synthesis of isatin thiosemicarbazones derivatives: in vitro anti-cancer, DNA binding and cleavage activities
    Ali AQ, Teoh SG, Salhin A, Eltayeb NE, Khadeer Ahamed MB, Abdul Majid AM
    Spectrochim Acta A Mol Biomol Spectrosc, 2014 May 5;125:440-8.
    PMID: 24607427 DOI: 10.1016/j.saa.2014.01.086
    New derivatives of thiosemicarbazone Schiff base with isatin moiety were synthesized L1-L6. The structures of these compounds were characterized based on the spectroscopic techniques. Compound L6 was further characterized by XRD single crystal. The interaction of these compounds with calf thymus (CT-DNA) exhibited high intrinsic binding constant (k(b)=5.03-33.00×10(5) M(-1)) for L1-L3 and L5 and (6.14-9.47×10(4) M(-1)) for L4 and L6 which reflect intercalative activity of these compounds toward CT-DNA. This result was also confirmed by the viscosity data. The electrophoresis studies reveal the higher cleavage activity of L1-L3 than L4-L6. The in vitro anti-proliferative activity of these compounds against human colon cancer cell line (HCT 116) revealed that the synthesized compounds (L3, L6 and L2) exhibited good anticancer potency.
    Matched MeSH terms: Cell Proliferation/drug effects
  17. Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II
    Bera H, Ojha Pk, Tan BJ, Sun L, Dolzhenko AV, Chui WK, et al.
    Eur J Med Chem, 2014 May 6;78:294-303.
    PMID: 24686016 DOI: 10.1016/j.ejmech.2014.03.063
    In our drug discovery program, a series of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones were designed, synthesized and evaluated for their TP inhibitory potential. All the synthesized analogues conferred a varying degree of TP inhibitory activity, comparable or better than positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 μM). A systematic approach to the lead optimization identified compounds 3c and 4a as the most promising TP inhibitors, exhibiting mixed mode of enzyme inhibition. Moreover, selected compounds demonstrated the ability to attenuate the expression of the angiogenic markers (viz. MMP-9 and VEGF) in MDA-MB-231 cells at sublethal concentrations. In addition, molecular docking studies revealed the plausible binding orientation of these inhibitors towards TP, which was in accordance with the experimental results. Taken as a whole, these compounds would constitute a new direction for the design of novel TP inhibitors with promising antiangiogenic properties.
    Matched MeSH terms: Cell Proliferation/drug effects
  18. Impact of low oxygen tension on stemness, proliferation and differentiation potential of human adipose-derived stem cells
    Choi JR, Pingguan-Murphy B, Wan Abas WA, Noor Azmi MA, Omar SZ, Chua KH, et al.
    Biochem Biophys Res Commun, 2014 May 30;448(2):218-24.
    PMID: 24785372 DOI: 10.1016/j.bbrc.2014.04.096
    Adipose-derived stem cells (ASCs) have been found adapted to a specific niche with low oxygen tension (hypoxia) in the body. As an important component of this niche, oxygen tension has been known to play a critical role in the maintenance of stem cell characteristics. However, the effect of O2 tension on their functional properties has not been well determined. In this study, we investigated the effects of O2 tension on ASCs stemness, differentiation and proliferation ability. Human ASCs were cultured under normoxia (21% O2) and hypoxia (2% O2). We found that hypoxia increased ASC stemness marker expression and proliferation rate without altering their morphology and surface markers. Low oxygen tension further enhances the chondrogenic differentiation ability, but reduces both adipogenic and osteogenic differentiation potential. These results might be correlated with the increased expression of HIF-1α under hypoxia. Taken together, we suggest that growing ASCs under 2% O2 tension may be important in expanding ASCs effectively while maintaining their functional properties for clinical therapy, particularly for the treatment of cartilage defects.
    Matched MeSH terms: Cell Proliferation/drug effects
  19. Cytotoxic benzophenone and triterpene from Garcinia hombroniana
    Jamila N, Khairuddean M, Yaacob NS, Kamal NN, Osman H, Khan SN, et al.
    Bioorg Chem, 2014 Jun;54:60-7.
    PMID: 24813683 DOI: 10.1016/j.bioorg.2014.04.003
    Garcinia hombroniana (seashore mangosteen) in Malaysia is used to treat itching and as a protective medicine after child birth. This study was aimed to investigate the bioactive chemical constituents of the bark of G. hombroniana. Ethyl acetate and dichloromethane extracts of G. hombroniana yielded two new (1, 9) and thirteen known compounds which were characterized by the spectral techniques of NMR, UV, IR and EI/ESI-MS, and identified as; 2,3',4,5'-tetrahydroxy-6-methoxybenzophenone(1), 2,3',4,4'-tetrahydroxy-6-methoxybenzophenone (2), 2,3',4,6-tetrahydroxybenzophenone (3), 1,3,6,7-tetrahydroxyxanthone (4), 3,3',4',5,7-pentahydroxyflavone (5),3,3',5,5',7-pentahydroxyflavanone (6), 3,3',4',5,5',7-hexahydroxyflavone (7), 4',5,7-trihydroxyflavanone-7-rutinoside (8), 18(13→17)-abeo-3β-acetoxy-9α,13β-lanost-24E-en-26-oic acid (9), garcihombronane B (10), garcihombronane D (11), friedelan-3-one (12), lupeol (13), stigmasterol (14) and stigmasterol glucoside (15). In the in vitro cytotoxicity against MCF-7, DBTRG, U2OS and PC-3 cell lines, compounds 1 and 9 displayed good cytotoxic effects against DBTRG cancer cell lines. Compounds 1-8 were also found to possess significant antioxidant activities. Owing to these properties, this study can be further extended to explore more significant bioactive components of this plant.
    Matched MeSH terms: Cell Proliferation/drug effects
  20. Fulltext Inhibition of Egr1 expression underlies the anti-mitogenic effects of cAMP in vascular smooth muscle cells
    Kimura TE, Duggirala A, Hindmarch CC, Hewer RC, Cui MZ, Newby AC, et al.
    J Mol Cell Cardiol, 2014 Jul;72(100):9-19.
    PMID: 24534707 DOI: 10.1016/j.yjmcc.2014.02.001
    AIMS: Cyclic AMP inhibits vascular smooth muscle cell (VSMC) proliferation which is important in the aetiology of numerous vascular diseases. The anti-mitogenic properties of cAMP in VSMC are dependent on activation of protein kinase A (PKA) and exchange protein activated by cAMP (EPAC), but the mechanisms are unclear.

    METHODS AND RESULTS: Selective agonists of PKA and EPAC synergistically inhibited Egr1 expression, which was essential for VSMC proliferation. Forskolin, adenosine, A2B receptor agonist BAY60-6583 and Cicaprost also inhibited Egr1 expression in VSMC but not in endothelial cells. Inhibition of Egr1 by cAMP was independent of cAMP response element binding protein (CREB) activity but dependent on inhibition of serum response element (SRE) activity. SRF binding to the Egr1 promoter was not modulated by cAMP stimulation. However, Egr1 expression was dependent on the SRF co-factors Elk1 and 4 but independent of MAL. Inhibition of SRE-dependent Egr1 expression was due to synergistic inhibition of Rac1 activity by PKA and EPAC, resulting in rapid cytoskeleton remodelling and nuclear export of ERK1/2. This was associated with de-phosphorylation of the SRF co-factor Elk1.

    CONCLUSION: cAMP inhibits VSMC proliferation by rapidly inhibiting Egr1 expression. This occurs, at least in part, via inhibition of Rac1 activity leading to rapid actin-cytoskeleton remodelling, nuclear export of ERK1/2, impaired Elk1-phosphorylation and inhibition of SRE activity. This identifies one of the earliest mechanisms underlying the anti-mitogenic effects of cAMP in VSMC but not in endothelial cells, making it an attractive target for selective inhibition of VSMC proliferation.

    Matched MeSH terms: Cell Proliferation/drug effects
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