Displaying publications 21 - 40 of 47 in total

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  1. Fulltext Aqueous fraction of Nephelium ramboutan-ake rind induces mitochondrial-mediated apoptosis in HT-29 human colorectal adenocarcinoma cells
    Chan CK, Goh BH, Kamarudin MN, Kadir HA
    Molecules, 2012 May 31;17(6):6633-57.
    PMID: 22728359 DOI: 10.3390/molecules17066633
    The aim of this study was to investigate the cytotoxic and apoptotic effects of Nephelium ramboutan-ake (pulasan) rind in selected human cancer cell lines. The crude ethanol extract and fractions (ethyl acetate and aqueous) of N. ramboutan-ake inhibited the growth of HT-29, HCT-116, MDA-MB-231, Ca Ski cells according to MTT assays. The N. ramboutan-ake aqueous fraction (NRAF) was found to exert the greatest cytotoxic effect against HT-29 in a dose-dependent manner. Evidence of apoptotic cell death was revealed by features such as chromatin condensation, nuclear fragmentation and apoptotic body formation. The result from a TUNEL assay strongly suggested that NRAF brings about DNA fragmentation in HT-29 cells. Phosphatidylserine (PS) externalization on the outer leaflet of plasma membranes was detected with annexin V-FITC/PI binding, confirming the early stage of apoptosis. The mitochondrial permeability transition is an important step in the induction of cellular apoptosis, and the results clearly suggested that NRAF led to collapse of mitochondrial transmembrane potential in HT-29 cells. This attenuation of mitochondrial membrane potential (Δψm) was accompanied by increased production of ROS and depletion of GSH, an increase of Bax protein expression, and induced-activation of caspase-3/7 and caspase-9. These combined results suggest that NRAF induces mitochondrial-mediated apoptosis.
    Matched MeSH terms: Enzyme Activation/drug effects
  2. Effects of glycyrrhizic acid on 11 β-hydroxysteroid dehydrogenase (11 βHSD1 and 2) activities and HOMA-IR in rats at different treatment periods
    Chia YY, Yin YY, Ton SH, Kadir KB
    Exp. Clin. Endocrinol. Diabetes, 2010 Oct;118(9):617-24.
    PMID: 19998240 DOI: 10.1055/s-0029-1237703
    Glycyrrhizic acid (GA) has been reported to inhibit postprandial blood glucose rise and 11 β-hydroxysteroid dehydrogenase 1 (11 βHSD1) activity. As not much work has been done on GA effects on 11 βHSD1 and 2 and HOMA-IR at different treatment periods, this work was conducted. 60 male Sprague Dawley rats fed AD LIBITUM were assigned into six groups of control and treated that were given GA at different duration namely 12, 24 and 48 h. Treated and control groups were intraperitoneally administered with GA (50 mgkg (-1)) and saline respectively. Blood and subcutaneous (ATS) and visceral adipose tissue (ATV), abdominal (MA) and quadriceps femoris muscle (MT), liver (L) and kidney (K) were examined. HOMA-IR in GA-treated rats decreased in all groups (P<0.05). In the 12-h and 24-h treated rats, 11 βHSD1 activities decreased in all tissues (P<0.05) except MA and MT (P>0.05) in the former and ATV (P>0.05) in the latter. However, 11 βHSD1 activities decreased significantly in all tissues ( P<0.05) in the 48-h treated rats. Significant decrease in 11 βHSD2 (P>0.05) activities were observed in the L of all treatment groups and K in the 24-h and 48-h treated rats (P<0.05). Histological analysis on ATS showed increase in the number of small-size adipocytes while ATV adipocytes showed shrinkage after GA administration. Increased glycogen deposition in the L was observed in the GA-administered rats in all the treatment periods. In conclusion, GA treatment showed a decrease in the HOMA-IR and both 11 βHSD1 and 2 activities in all tissues, with more profound decrease in the 48-h treated rats.
    Matched MeSH terms: Enzyme Activation/drug effects
  3. Synthesis of novel derivatives of oxindole, their urease inhibition and molecular docking studies
    Taha M, Ismail NH, Khan A, Shah SA, Anwar A, Halim SA, et al.
    Bioorg Med Chem Lett, 2015 Aug 15;25(16):3285-9.
    PMID: 26077497 DOI: 10.1016/j.bmcl.2015.05.069
    We synthesized a series of novel 5-24 derivatives of oxindole. The synthesis started from 5-chlorooxindole, which was condensed with methyl 4-carboxybezoate and result in the formation of benzolyester derivatives of oxindole which was then treated with hydrazine hydrate. The oxindole benzoylhydrazide was treated with aryl acetophenones and aldehydes to get target compounds 5-24. The synthesized compounds were evaluated for urease inhibition; the compound 5 (IC50 = 13.00 ± 0.35 μM) and 11 (IC50 = 19.20 ± 0.50 μM) showed potent activity as compared to the standard drug thiourea (IC50 = 21.00 ± 0.01 μM). Other compounds showed moderate to weak activity. All synthetic compounds were characterized by different spectroscopic techniques including (1)H NMR, (13)C NMR, IR and EI MS. The molecular interactions of the active compounds within the binding site of urease enzyme were studied through molecular docking simulations.
    Matched MeSH terms: Enzyme Activation/drug effects
  4. Effects of iridoids on lipoxygenase and hyaluronidase activities and their activation by beta-glucosidase in the presence of amino acids
    Ling SK, Tanaka T, Kouno I
    Biol Pharm Bull, 2003 Mar;26(3):352-6.
    PMID: 12612446
    Enzyme inhibitory activities of 14 iridoids previously obtained from two Malaysian medicinal plants, Saprosma scortechinii and Rothmannia macrophylla, were evaluated in vitro using soybean lipoxygenase and bovine testis hyaluronidase. Most of the iridoids, including asperulosidic acid, paederosidic acid, and an epimeric mixture of gardenogenins A and B, did not show any effect on the enzyme activities, except for the bis-iridoids, which inhibited the lipoxygenase activity with their IC(50) values of approximately 1.3 times that of a known inhibitor, fisetin. Structural modification of asperulosidic acid and paederosidic acid through enzymatic hydrolysis by beta-glucosidase resulted in their inhibition towards the enzyme activities, and these activities were enhanced by the presence of some amino acids (lysine, leucine or glutamic acid) or ammonium acetate. Mixtures of gardenogenins A and B; isomers of non-glucosidic iridoids, incubated with amino acid or ammonium acetate did not show any inhibitory effect on the enzyme activities during the 6 h incubation period, except for lysine where spontaneous reaction between the iridoids and amino acid resulted in the inhibition of lipoxygenase activity. The results from these biomimetic reactions suggested that the iridoid aglycons and the intermediates formed by these reactive species could inhibit the enzyme activities, and thus substantiate previous reports that the formation of iridoidal aglycons is a prerequisite for the iridoid glycosides to demonstrate some of the biological activities. In addition, the results also indicated that it is worthwhile to further explore these intermediates as potential anti-inflammatory agents.
    Matched MeSH terms: Enzyme Activation/drug effects
  5. Fulltext Purification and Characterization of Lipase Produced by Leuconostoc mesenteroides Subsp. mesenteroides ATCC 8293 Using an Aqueous Two-Phase System (ATPS) Composed of Triton X-100 and Maltitol
    Eko Sukohidayat NH, Zarei M, Baharin BS, Manap MY
    Molecules, 2018 Jul 20;23(7).
    PMID: 30037038 DOI: 10.3390/molecules23071800
    Purification of lipase produced by L. mesenteroides subsp. mesenteroides ATCC 8293 was conducted for the first time using a novel aqueous two-phase system (ATPS) composed of Triton X-100 and maltitol. The partitioning of lipase was optimized according to several parameters including pH, temperature, and crude load. Results showed that lipase preferentially migrated to the Triton X-100 rich phase and optimum lipase partitioning was achieved in ATPS at TLL of 46.4% and crude load of 20% at 30 °C and pH 8, resulting in high lipase purification factor of 17.28 and yield of 94.7%. The purified lipase showed a prominent band on SDS-PAGE with an estimated molecular weight of 50 kDa. The lipase was stable at the temperature range of 30⁻60 °C and pH range of 6⁻11, however, it revealed its optimum activity at the temperature of 37 °C and pH 8. Moreover, lipase exhibited enhanced activity in the presence of non-ionic surfactants with increased activity up to 40%. Furthermore, results exhibited that metals ions such as Na⁺, Mg2+, K⁺ and Ca2+ stimulated lipase activity. This study demonstrated that this novel system could be potentially used as an alternative to traditional ATPS for the purification and recovery of enzymes since the purified lipase still possesses good process characteristics after undergoing the purification process.
    Matched MeSH terms: Enzyme Activation/drug effects
  6. Fulltext In Vitro antioxidant and xanthine oxidase inhibitory activities of methanolic Swietenia mahagoni seed extracts
    Sahgal G, Ramanathan S, Sasidharan S, Mordi MN, Ismail S, Mansor SM
    Molecules, 2009 Nov 06;14(11):4476-85.
    PMID: 19924080 DOI: 10.3390/molecules14114476
    This study examines the in vitro antioxidant activities of the methanol extract of Swietenia mahagoni seeds (SMCM seed extract). The extract was screened for possible antioxidant activities by free radical scavenging activity (DPPH), xanthine oxidase inhibition (XOI), hydrogen peroxide scavenging activity (HPSA) and ferric-reducing antioxidant power (FRAP) assays. The total phenolic and flavonoid contents were also determined. The extract exhibits antioxidant activity of 23.29% with an IC(50 )value of 2.3 mg/mL in the DPPH radical scavenging method, 47.2% in the XOI assay, 49.5% by the HPSA method, and 0.728 mmol/Fe(II)g in the FRAP method at the concentration tested. The amount of total phenolics and flavonoid contents was 70.83 mg gallic acid equivalent (GAE) and 2.5 +/- 0.15 mg of catechin equivalent per gram of dry extract, respectively. High Performance Thin Layer Chromatography (HPTLC) screening indicates the presence of phenolic compounds in the SMCM seed extract. The results indicate that the extract has both high free radical scavenging and xanthine oxidase inhibition activity. The antioxidant activity of SMCM seed extract is comparable with that of other Malaysian tropical fruits and herbal plants.
    Matched MeSH terms: Enzyme Activation/drug effects*
  7. Fulltext Synthesis of chalcones with anticancer activities
    Syam S, Abdelwahab SI, Al-Mamary MA, Mohan S
    Molecules, 2012 May 25;17(6):6179-95.
    PMID: 22634834 DOI: 10.3390/molecules17066179
    Several chalcones were synthesized and their in vitro cytotoxicity against various human cell lines, including human breast adenocarcinoma cell line MCF-7, human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3, human adenocarcinoma cell line HT-29 (colorectal cancer) and human normal liver cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic agents, four of them with minimal IC₅₀ values were chosen and studied in detail with MCF-7 cells. The compounds 1, 5, 23, and 25 were capable in eliciting apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and caspase-3/7, -8, and -9 activities (p < 0.05). The ROS level showed 1.3-fold increase (p < 0.05) at the low concentrations used and thus it was concluded that the compounds increased the ROS level eventually leading to apoptosis in MCF-7 cells through intrinsic as well as extrinsic pathways.
    Matched MeSH terms: Enzyme Activation/drug effects
  8. Synthesis and cholinesterase inhibitory activity study of new piperidone grafted spiropyrrolidines
    Basiri A, Abd Razik BM, Ezzat MO, Kia Y, Kumar RS, Almansour AI, et al.
    Bioorg Chem, 2017 12;75:210-216.
    PMID: 28987876 DOI: 10.1016/j.bioorg.2017.09.019
    Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, which affected 35 million people in the world. The most practiced approach to improve the life expectancy of AD patients is to increase acetylcholine neurotransmitter level at cholinergic synapses by inhibition of cholinesterase enzymes. A series of unreported piperidone grafted spiropyrrolidines 8(a-p) were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Therein, compounds 8h and 8l displayed more potent AChE enzyme inhibition than standard drug with IC50 values of 1.88 and 1.37 µM, respectively. Molecular docking simulations for 8l possessing the most potent AChE inhibitory activities, disclosed its interesting binding templates to the active site channel of AChE enzymes. These compounds are remarkable AChE inhibitors and have potential as AD drugs.
    Matched MeSH terms: Enzyme Activation/drug effects
  9. Fulltext Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells
    Lee ST, Wong PF, Cheah SC, Mustafa MR
    PLoS One, 2011;6(4):e18915.
    PMID: 21541327 DOI: 10.1371/journal.pone.0018915
    Alpha-tomatine (α-tomatine) is the major saponin in tomato (Lycopersicon esculentum). This study investigates the chemopreventive potential of α-tomatine on androgen-independent human prostatic adenocarcinoma PC-3 cells.
    Matched MeSH terms: Enzyme Activation/drug effects
  10. Fulltext Sodium nitrite exerts an antihypertensive effect and improves endothelial function through activation of eNOS in the SHR
    Ling WC, Murugan DD, Lau YS, Vanhoutte PM, Mustafa MR
    Sci Rep, 2016 09 12;6:33048.
    PMID: 27616322 DOI: 10.1038/srep33048
    Sodium nitrite (NaNO2) induces relaxation in isolated arteries partly through an endothelium-dependent mechanism involving NO-eNOS-sGC-cGMP pathway. The present study was designed to investigate the effect of chronic NaNO2 administration on arterial systolic blood pressure (SBP) and vascular function in hypertensive rats. NaNO2 (150 mg L-1) was given in drinking water for four weeks to spontaneously (SHR) and Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) treated hypertensive SD rats. Arterial SBP and vascular function in isolated aortae were studied. Total plasma nitrate/nitrite and vascular cyclic guanosine monophosphate (cGMP) levels were measured using commercially available assay kits. Vascular nitric oxide (NO) levels were evaluated by DAF-FM fluorescence while the proteins involved in endothelial nitric oxide synthase (eNOS) activation was determined by Western blotting. NaNO2 treatment reduced SBP, improved the impaired endothelium-dependent relaxation, increased plasma total nitrate/nitrite level and vascular tissue NO and cGMP levels in SHR. Furthermore, increased presence of phosphorylated eNOS and Hsp-90 was observed in NaNO2-treated SHR. The beneficial effect of nitrite treatment was not observed in L-NAME treated hypertensive SD rats. The present study provides evidence that chronic treatment of genetically hypertensive rats with NaNO2 improves endothelium-dependent relaxation in addition to its antihypertensive effect, partly through mechanisms involving activation of eNOS.
    Matched MeSH terms: Enzyme Activation/drug effects
  11. Fulltext In vitro and in vivo anti-angiogenic activities of Panduratin A
    Lai SL, Cheah SC, Wong PF, Noor SM, Mustafa MR
    PLoS One, 2012;7(5):e38103.
    PMID: 22666456 DOI: 10.1371/journal.pone.0038103
    BACKGROUND: Targeting angiogenesis has emerged as an attractive and promising strategy in anti-cancer therapeutic development. The present study investigates the anti-angiogenic potential of Panduratin A (PA), a natural chalcone isolated from Boesenbergia rotunda by using both in vitro and in vivo assays.

    METHODOLOGY/PRINCIPAL FINDINGS: PA exerted selective cytotoxicity on human umbilical vein endothelial cells (HUVECs) with IC(50) value of 6.91 ± 0.85 µM when compared to human normal fibroblast and normal liver epithelial cells. Assessment of the growth kinetics by cell impedance-based Real-Time Cell Analyzer showed that PA induced both cytotoxic and cytostatic effects on HUVECs, depending on the concentration used. Results also showed that PA suppressed VEGF-induced survival and proliferation of HUVECs. Furthermore, endothelial cell migration, invasion, and morphogenesis or tube formation demonstrated significant time- and dose-dependent inhibition by PA. PA also suppressed matrix metalloproteinase-2 (MMP-2) secretion and attenuated its activation to intermediate and active MMP-2. In addition, PA suppressed F-actin stress fiber formation to prevent migration of the endothelial cells. More importantly, anti-angiogenic potential of PA was also evidenced in two in vivo models. PA inhibited neo-vessels formation in murine Matrigel plugs, and angiogenesis in zebrafish embryos.

    CONCLUSIONS/SIGNIFICANCE: Taken together, our study demonstrated the distinctive anti-angiogenic properties of PA, both in vitro and in vivo. This report thus reveals another biological activity of PA in addition to its reported anti-inflammatory and anti-cancer activities, suggestive of PA's potential for development as an anti-angiogenic agent for cancer therapy.

    Matched MeSH terms: Enzyme Activation/drug effects
  12. Fulltext Inhibition of mitochondrial cytochrome c release and suppression of caspases by gamma-tocotrienol prevent apoptosis and delay aging in stress-induced premature senescence of skin fibroblasts
    Makpol S, Abdul Rahim N, Hui CK, Ngah WZ
    Oxid Med Cell Longev, 2012;2012:785743.
    PMID: 22919441 DOI: 10.1155/2012/785743
    In this study, we determined the molecular mechanism of γ-tocotrienol (GTT) in preventing cellular aging by focusing on its anti-apoptotic effect in stress-induced premature senescence (SIPS) model of human diploid fibroblasts (HDFs). Results obtained showed that SIPS exhibited senescent-phenotypic characteristic, increased expression of senescence-associated β-galactosidase (SA β-gal) and promoted G(0)/G(1) cell cycle arrest accompanied by shortening of telomere length with decreased telomerase activity. Both SIPS and senescent HDFs shared similar apoptotic changes such as increased Annexin V-FITC positive cells, increased cytochrome c release and increased activation of caspase-9 and caspase-3 (P < 0.05). GTT treatment resulted in a significant reduction of Annexin V-FITC positive cells, inhibited cytochrome c release and decreased activation of caspase-9 and caspase-3 (P < 0.05). Gene expression analysis showed that GTT treatment down regulated BAX mRNA, up-regulated BCL2A1 mRNA and decreased the ratio of Bax/Bcl-2 protein expression (P < 0.05) in SIPS. These findings suggested that GTT inhibits apoptosis by modulating the upstream apoptosis cascade, causing the inhibition of cytochrome c release from the mitochondria with concomitant suppression of caspase-9 and caspase-3 activation. In conclusion, GTT delays cellular senescence of human diploid fibroblasts through the inhibition of intrinsic mitochondria-mediated pathway which involved the regulation of pro- and anti-apoptotic genes and proteins.
    Matched MeSH terms: Enzyme Activation/drug effects
  13. Fulltext gamma-Tocotrienol prevents oxidative stress-induced telomere shortening in human fibroblasts derived from different aged individuals
    Makpol S, Abidin AZ, Sairin K, Mazlan M, Top GM, Ngah WZ
    Oxid Med Cell Longev, 2010 Jan-Feb;3(1):35-43.
    PMID: 20716926 DOI: 10.4161/oxim.3.1.9940
    The effects of palm gamma-tocotrienol (GGT) on oxidative stress-induced cellular ageing was investigated in normal human skin fibroblast cell lines derived from different age groups; young (21-year-old, YF), middle (40-year-old, MF) and old (68-year-old, OF). Fibroblast cells were treated with gamma-tocotrienol for 24 hours before or after incubation with IC50 dose of H2O2 for 2 hours. Changes in cell viability, telomere length and telomerase activity were assessed using the MTS assay (Promega, USA), Southern blot analysis and telomere repeat amplification protocol respectively. Results showed that treatment with different concentrations of gamma-tocotrienol increased fibroblasts viability with optimum dose of 80 microM for YF and 40 microM for both MF and OF. At higher concentrations, gamma-tocotrienol treatment caused marked decrease in cell viability with IC50 value of 200 microM (YF), 300 microM (MF) and 100 microM (OF). Exposure to H2O2 decreased cell viability in dose dependent manner, shortened telomere length and reduced telomerase activity in all age groups. The IC50 of H2O2 was found to be; YF (700 microM), MF (400 microM) and OF (100 microM). Results showed that viability increased significantly (p < 0.05) when cells were treated with 80 microM and 40 microM gamma-tocotrienol prior or after H2O2-induced oxidative stress in all age groups. In YF and OF, pretreatment with gamma-tocotrienol prevented shortening of telomere length and reduction in telomerase activity. In MF, telomerase activity increased while no changes in telomere length was observed. However, post-treatment of gamma-tocotrienol did not exert any significant effects on telomere length and telomerase activity. Thus, these data suggest that gamma-tocotrienol protects against oxidative stress-induced cellular ageing by modulating the telomere length possibly via telomerase.
    Matched MeSH terms: Enzyme Activation/drug effects
  14. One-pot microwave assisted stereoselective synthesis of novel dihydro-2'H-spiro[indene-2,1'-pyrrolo-[3,4-c]pyrrole]-tetraones and evaluation of their antimycobacterial activity and inhibition of AChE
    Bharkavi C, Vivek Kumar S, Ashraf Ali M, Osman H, Muthusubramanian S, Perumal S
    Bioorg Med Chem Lett, 2017 Jul 15;27(14):3071-3075.
    PMID: 28552337 DOI: 10.1016/j.bmcl.2017.05.050
    An efficient one-pot microwave assisted stereoselective synthesis of novel dihydro-2'H-spiro[indene-2,1'-pyrrolo[3,4-c]pyrrole]-tetraone derivatives through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ from ninhydrin and sarcosine with a series of 1-aryl-1H-pyrrole-2,5-diones is described. The synthesised compounds were screened for their antimycobacterial and AChE inhibition activities. Compound 4b (IC50 1.30µM) has been found to display twelve fold antimycobacterial activity compared to cycloserine and it is thirty seven times more active than pyrimethamine. Compound 4h displays maximum AchE inhibitory activity with IC50 value of 0.78±0.01µmol/L.
    Matched MeSH terms: Enzyme Activation/drug effects
  15. Regulation of p53-, Bcl-2- and caspase-dependent signaling pathway in xanthorrhizol-induced apoptosis of HepG2 hepatoma cells
    Handayani T, Sakinah S, Nallappan M, Pihie AH
    Anticancer Res, 2007 Mar-Apr;27(2):965-71.
    PMID: 17465228
    Xanthorrhizol is a sesquiterpenoid compound extracted from the rhizome of Curcuma xanthorrhiza. This study investigated the antiproliferative effect and the mechanism of action of xanthorrhizol on human hepatoma cells, HepG2, and the mode of cell death. An antiproliferative assay using methylene blue staining revealed that xanthorrhizol inhibited the proliferation of the HepG2 cells with a 50% inhibition of cell growth (IC50) value of 4.17 +/- 0.053 microg/ml. The antiproliferative activity of xanthorrhizol was due to apoptosis induced in the HepG2 cells and not necrosis, which was confirmed by the Tdt-mediated dUTP nick end labeling (TUNEL) assay. The xanthorrhizol-treated HepG2 cells showed typical apoptotic morphology such as DNA fragmentation, cell shrinkage and elongated lamellipodia. The apoptosis mediated by xanthorrhizol in the HepG2 cells was associated with the activation of tumor suppressor p53 and down-regulation of antiapoptotic Bcl-2 protein expression, but not Bax. The levels of Bcl-2 protein expression decreased 24-h after treatment with xanthorrhizol and remained lower than controls throughout the experiment, resulting in a shift in the Bax to Bcl-2 ratio thus favouring apoptosis. The processing of the initiator procaspase-9 was detected. Caspase-3 was also found to be activated, but not caspase-7. Xanthorrhizol exerts antiproliferative effects on HepG2 cells by inducing apoptosis via the mitochondrial pathway.
    Matched MeSH terms: Enzyme Activation/drug effects
  16. Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells
    Inayat-Hussain SH, Annuar BO, Din LB, Ali AM, Ross D
    Toxicol In Vitro, 2003 Aug;17(4):433-9.
    PMID: 12849726
    Styryl-lactones such as goniothalamin represent a new class of compounds with potential anti-cancer properties. In this study, we investigated the mechanisms of goniothalamin (GTN), a plant styryl-lactone induced apoptosis in human promyelocytic leukemia HL-60 cells. This plant extract resulted in apoptosis in HL-60 cells as assessed by the externalisation of phosphatidylserine. Using the mitochondrial membrane dye (DIOC(6)) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Deltapsi(m)). Further immunoblotting on these cells showed activation of initiator caspase-9 and the executioner caspases-3 and -7. Pretreatment with the pharmacological caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) abrogated apoptosis as assessed by all of the apoptotic features in this study. In summary, our results demonstrate that goniothalamin-induced apoptosis occurs via the mitochondrial pathway in a caspase dependent manner.
    Matched MeSH terms: Enzyme Activation/drug effects
  17. Fulltext The anti-proliferative effects of a palm oil-derived product and its mode of actions in human malignant melanoma MeWo cells
    Komarasamy TV, Sekaran SD
    J Oleo Sci, 2012;61(4):227-39.
    PMID: 22450124
    Melanoma incidence and mortality have risen dramatically in recent years. No effective treatment for metastatic melanoma exists; hence currently, an intense effort for new drug evaluation is being carried out. In this study, we investigated the effects of a palm oil-derived nanopolymer called Bio-12 against human malignant melanoma. The nanopolymers of Bio-12 are lipid esters derived from a range of fatty acids of palm oil. Our study aims to identify the anti-proliferative properties of Bio-12 against human malignant melanoma cell line (MeWo) and to elucidate the mode of actions whereby Bio-12 brings about cell death. Bio-12 significantly inhibited the growth of MeWo cells in a concentration- and time- dependent manner with a median inhibitory concentration (IC₅₀) value of 1/25 dilution after 72 h but was ineffective on human normal skin fibroblasts (CCD-1059sk). We further investigated the mode of actions of Bio-12 on MeWo cells. Cell cycle flow cytometry demonstrated that MeWo cells treated with increasing concentrations of Bio-12 resulted in S-phase arrest, accompanied by the detection of sub-G1 content, indicative of apoptotic cell death. Induction of apoptosis was further confirmed via caspase (substrate) cleavage assay which showed induction of early apoptosis in MeWo cells. In addition, DNA strand breaks which are terminal event in apoptosis were evident through increase of TUNEL positive cells and formation of a characteristic DNA ladder on agarose gel electrophoresis. Moreover, treatment of MeWo cells with Bio-12 induced significant increase in lactate dehydrogenase (LDH) activity. These results show that Bio-12 possesses the ability to suppress proliferation of human malignant melanoma MeWo cells and this suppression is at least partly attributed to the initiation of the S-phase arrest, apoptosis and necrosis, suggesting that it is indeed worth for further investigations.
    Matched MeSH terms: Enzyme Activation/drug effects
  18. Arginase activity in a murine macrophage cell line (RAW264.7) stimulated with lipopolysaccharide from Actinobacillus actinomycetemcomitans
    Sosroseno W, Musa M, Ravichandran M, Fikri Ibrahim M, Bird PS, Seymour GJ
    Oral Microbiol. Immunol., 2006 Jun;21(3):145-50.
    PMID: 16626370
    The aim of the present study was to determine whether or not lipopolysaccharide from Actinobacillus actinomycetemcomitans could stimulate arginase activity in a murine macrophage cell line (RAW264.7 cells).
    Matched MeSH terms: Enzyme Activation/drug effects
  19. α-Glucosidase activity of oleanolic acid and its oxidative metabolites: DFT and Docking studies
    Anouar el H, Zakaria NS, Alsalme A, Shah SA
    Mini Rev Med Chem, 2015;15(14):1148-58.
    PMID: 26205959
    A natural pentacyclic triterpenoid oleanolic acid 1 and its biotransformed metabolites 2-3 are potential α-glucosidase inhibitors. To elucidate the inhibitory mechanism of compounds 1, 2 and 3 against α-glucosidase, we calculated (i) their electronic and optical properties using DFT and TD-DFT at the B3LYP/6-31G(d) level in gas and IEF-PCM solvent; and (ii) their binding energies to α-glucosidase via docking study. DFT results showed that the α-glucosidase inhibtion is mainly depend on the polarity parameters of the studied compounds. Docking results revealed that the activity increased with binding energies (i.e. the stability of ligand-receptor complex). The specroscopic data of oleanolic acid 1 and its metabolites 2 and 3 are well predicetd for 13C NMR chemical shifts (R2=99%) and 1H NMR chemical shifts (R2=90%); and for (ii) UV/vis spectra. The assignments and interpretation of NMR chemical shifts and bathochromic shift of λMAX absorption bands are discussed.
    Matched MeSH terms: Enzyme Activation/drug effects
  20. Antiproliferation effect of guanosine on HCT 116 cells involves MAPK and AMPK pathways
    Teoh WY, Wahab NA, Sim KS
    Nucleosides Nucleotides Nucleic Acids, 2017 Apr 03;36(4):243-255.
    PMID: 28323520 DOI: 10.1080/15257770.2016.1268693
    This study aims to investigate the mechanisms associated with the antiproliferation effect of guanosine on human colon carcinoma HCT 116 cells. In this study, guanosine induced more drastic cell cycle arrest effect than cell death effect on HCT 116 cells. The cell cycle arrest effect of guanosine on HCT 116 cells appeared to be associated with the increased activation of mitogen-activated protein kinases (MAPK) such as ERK1/2, p38 and JNK. The decrease of AMP-activated protein kinase (AMPK) activation and cyclin D1 expression was also involved. Thus, the antiproliferation of colon cancer cells of guanosine could be mediated by the disruption of MAPK and AMPK pathways.
    Matched MeSH terms: Enzyme Activation/drug effects
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