Displaying publications 1 - 20 of 39 in total

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  1. Yeong KY, Tan SC, Mai CW, Leong CO, Chung FF, Lee YK, et al.
    Chem Biol Drug Des, 2018 01;91(1):213-219.
    PMID: 28719017 DOI: 10.1111/cbdd.13072
    Both sirtuin and poly(ADP-ribose)polymerase (PARP) family of enzymes utilize NAD+ as co-substrate. Inhibitors of sirtuins and PARPs are important tools in drug discovery as they are reported to be linked to multiple diseases such as cancer. New potent sirtuin inhibitors (2,4,6-trisubstituted benzimidazole) were discovered from reported PARP inhibitor scaffold. Interestingly, the synthesized compounds have contrasting sirtuin and PARP-1 inhibitory activities. We showed that modification on benzimidazoles may alter their selectivity toward sirtuin or PARP-1 enzymes. This offers an opportunity for further discovery and development of new promising sirtuin inhibitors. Molecular docking studies were carried out to aid the rationalization of these observations. Preliminary antiproliferative studies of selected compounds against nasopharyngeal cancer cells also showed relatively promising results.
    Matched MeSH terms: Adenosine Diphosphate Ribose
  2. Nwaefulu ON, Al-Shar'i NA, Owolabi JO, Sagineedu SR, Woei LC, Wai LK, et al.
    J Mol Model, 2022 Oct 04;28(11):340.
    PMID: 36194315 DOI: 10.1007/s00894-022-05326-1
    Cancer is imposing a global health burden because of the steady increase in new cases. Moreover, current anticancer therapeutics are associated with many drawbacks, mainly the emergence of resistance and the severe adverse effects. Therefore, there is a continuous need for developing new anticancer agents with novel mechanisms of action and lower side effects. Natural products have been a rich source of anticancer medication. Cycleanine, a natural product, was reported to exert an antiproliferative effect on ovarian cancer cells by causing apoptosis through activation of caspases 3/7 and cleavage of poly (ADP-ribose) polymerase to form poly (ADP-ribose) polymerase-1 (PARP1). It is well-established that PARP1 is associated with carcinogenesis, and different PARP1 inhibitors are approved as anticancer drugs. In this study, the cytotoxic activity of cycleanine was computationally investigated to determine whether it is a PARP1 inhibitor or a caspase activator. Molecular docking and molecular dynamics (MD) simulations were utilized for this purpose. The results showed that cycleanine has a good binding affinity to PARP1; moreover, MD simulation showed that it forms a stable complex with the enzyme. Consequently, the results showed that cycleanine is a potential inhibitor of the PARP1 enzyme.
    Matched MeSH terms: Poly(ADP-ribose) Polymerase Inhibitors/pharmacology; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use; Poly(ADP-ribose) Polymerases/metabolism; Ribose; Poly (ADP-Ribose) Polymerase-1
  3. Yusoh NA, Ahmad H, Gill MR
    ChemMedChem, 2020 Nov 18;15(22):2121-2135.
    PMID: 32812709 DOI: 10.1002/cmdc.202000391
    Platinum drugs are heavily used first-line chemotherapeutic agents for many solid tumours and have stimulated substantial interest in the biological activity of DNA-binding metal complexes. These complexes generate DNA lesions which trigger the activation of DNA damage response (DDR) pathways that are essential to maintain genomic integrity. Cancer cells exploit this intrinsic DNA repair network to counteract many types of chemotherapies. Now, advances in the molecular biology of cancer has paved the way for the combination of DDR inhibitors such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) and agents that induce high levels of DNA replication stress or single-strand break damage for synergistic cancer cell killing. In this review, we summarise early-stage, preclinical and clinical findings exploring platinum and emerging ruthenium anti-cancer complexes alongside PARPi in combination therapy for cancer and also describe emerging work on the ability of ruthenium and gold complexes to directly inhibit PARP activity.
  4. Tan TC, AlKarkhi AF, Easa AM
    Food Chem, 2012 Oct 15;134(4):2430-6.
    PMID: 23442706 DOI: 10.1016/j.foodchem.2012.04.049
    The addition of ribose to bovine or porcine gelatine solutions followed by heating at 95 °C yielded brown solutions with different pH, colour (CIE L(*) and b(*)) and absorbance (A(420*) values. These differences were used for gelatine powder identification, differentiation and quality control. Differentiation analysis of the Maillard reaction parameters was conducted using cluster analysis (CA) and confidence intervals (CI). The potential use of the method as a quality control procedure was evaluated by using statistical process control (SPC). CA revealed that the two types of gelatine could be classified into two different groups. CI (95% confidence) revealed that the absorbance and colour values could be used as indicators for differentiation between the two types of gelatine because the intervals between the Maillard reaction parameters of the samples were far apart. The methodology demonstrated good reproducibility because it behaved predictably based on the X¯-S charts generated from the SPC charts.
    Matched MeSH terms: Ribose/chemistry*
  5. Subramaniam M, In LL, Kumar A, Ahmed N, Nagoor NH
    Sci Rep, 2016;6:19833.
    PMID: 26817684 DOI: 10.1038/srep19833
    Mycobacterium indicus pranii (MIP) is a non-pathogenic mycobacterium, which has been tested on several cancer types like lung and bladder where tumour regression and complete recovery was observed. In discovering the potential cytotoxic elements, a preliminary test was carried out using four different fractions consisting of live bacteria, culture supernatant, heat killed bacteria and heat killed culture supernatant of MIP against two human cancer cells A549 and CaSki by 3-(4,5-dimethyl thiazol)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptosis was investigated in MCF-7 and ORL-115 cancer cells by poly-(ADP-ribose) polymerase (PARP) and DNA fragmentation assays. Among four MIP fractions, only heat killed MIP fraction (HKB) showed significant cytotoxicity in various cancer cells with inhibitory concentration, IC50 in the range 5.6-35.0 μl/(1.0 × 10(6) MIP cells/ml), while cytotoxicity effects were not observed in the remaining fractions. HKB did not show cytotoxic effects on non-cancerous cells contrary to cancerous cells, suggesting its safe usage and ability to differentially recognize between these cells. Evaluation on PARP assay further suggested that cytotoxicity in cancer cells were potentially induced via caspase-mediated apoptosis. The cytotoxic and apoptotic effects of MIP HKB have indicated that this fraction can be a good candidate to further identify effective anti-cancer agents.
  6. Abdullah I, Chee CF, Lee YK, Thunuguntla SSR, Satish Reddy K, Nellore K, et al.
    Bioorg Med Chem, 2015 Aug 01;23(15):4669-4680.
    PMID: 26088338 DOI: 10.1016/j.bmc.2015.05.051
    Poly (ADP-ribose) polymerases (PARPs) play diverse roles in various cellular processes that involve DNA repair and programmed cell death. Amongst these polymerases is PARP-1 which is the key DNA damage-sensing enzyme that acts as an initiator for the DNA repair mechanism. Dihydroorotate dehydrogenase (DHODH) is an enzyme in the pyrimidine biosynthetic pathway which is an important target for anti-hyperproliferative and anti-inflammatory drug design. Since these enzymes share a common role in the DNA replication and repair mechanisms, it may be beneficial to target both PARP-1 and DHODH in attempts to design new anti-cancer agents. Benzimidazole derivatives have shown a wide variety of pharmacological activities including PARP and DHODH inhibition. We hereby report the design, synthesis and bioactivities of a series of benzimidazole derivatives as inhibitors of both the PARP-1 and DHODH enzymes.
  7. Xu-hui Zhang, Lei Liang, Xiao-yan Wang, Li Zhang, Yan-xin Zheng, Hong-zhu Deng, et al.
    Sains Malaysiana, 2016;45:109-113.
    We investigated the antitumor effects of the combination of matrine-a purified alkaloid extracted from Sophora flavescence-and 5-fluorouracil (5-FU) on SW480 cells. This combination inhibited the growth of SW480 cells in a synergistic or additive manner by disrupting their progression through the cell cycle. Exposure of SW480 cells to matrine and 5-FU was followed by an increased rate of expression for caspase-3, caspase-9 and poly-ADP ribose polymerase (PARP) and inhibited the subcutaneous transplantation of SW480 tumors into Balb/c nude mice. Histopathological analysis showed that this effect was most pronounced in the spleens of treated animals. Typical cytotoxic effects observed in 5-FU-treated mice included fibrosis and lymphopenia, whereas in mice treated with 5-FU combined with matrine, the spleen ultrastructure remained intact. These findings indicate that matrine may enhance the therapeutic effectiveness of 5-FU in SW480 tumors by enhancing apoptosis and overcome the threat to immunocompetence associated with 5-FU.
    Matched MeSH terms: Adenosine Diphosphate Ribose
  8. Yusoh NA, Chia SL, Saad N, Ahmad H, Gill MR
    Sci Rep, 2023 Jan 26;13(1):1456.
    PMID: 36702871 DOI: 10.1038/s41598-023-28454-x
    Poly(ADP-ribose) polymerase (PARP) are critical DNA repair enzymes that are activated as part of the DNA damage response (DDR). Although inhibitors of PARP (PARPi) have emerged as small molecule drugs and have shown promising therapeutic effects, PARPi used as single agents are clinically limited to patients with mutations in germline breast cancer susceptibility gene (BRCA). Thus, novel PARPi combination strategies may expand their usage and combat drug resistance. In recent years, ruthenium polypyridyl complexes (RPCs) have emerged as promising anti-cancer candidates due to their attractive DNA binding properties and distinct mechanisms of action. Previously, we reported the rational combination of the RPC DNA replication inhibitor [Ru(dppz)2(PIP)]2+ (dppz = dipyrido[3,2-a:2',3'-c]phenazine, PIP = 2-(phenyl)-imidazo[4,5-f][1,10]phenanthroline), "Ru-PIP", with the PARPi Olaparib in breast cancer cells. Here, we expand upon this work and examine the combination of Ru-PIP with Olaparib for synergy in lung cancer cells, including in 3D lung cancer spheroids, to further elucidate mechanisms of synergy and additionally assess toxicity in a zebrafish embryo model. Compared to single agents alone, Ru-PIP and Olaparib synergy was observed in both A549 and H1975 lung cancer cell lines with mild impact on normal lung fibroblast MRC5 cells. Employing the A549 cell line, synergy was confirmed by loss in clonogenic potential and reduced migration properties. Mechanistic studies indicated that synergy is accompanied by increased double-strand break (DSB) DNA damage and reactive oxygen species (ROS) levels which subsequently lead to cell death via apoptosis. Moreover, the identified combination was successfully able to inhibit the growth of A549 lung cancer spheroids and acute zebrafish embryos toxicity studies revealed that this combination showed reduced toxicity compared to single-agent Ru-PIP.
  9. Yusoh NA, Tiley PR, James SD, Harun SN, Thomas JA, Saad N, et al.
    J Med Chem, 2023 May 25;66(10):6922-6937.
    PMID: 37185020 DOI: 10.1021/acs.jmedchem.3c00322
    Synergistic drug combinations can extend the use of poly(ADP-ribose) polymerase inhibitors (PARPi) such as Olaparib to BRCA-proficient tumors and overcome acquired or de novo drug resistance. To identify new synergistic combinations for PARPi, we screened a "micro-library" comprising a mix of commercially available drugs and DNA-binding ruthenium(II) polypyridyl complexes (RPCs) for Olaparib synergy in BRCA-proficient triple-negative breast cancer cells. This identified three hits: the natural product Curcumin and two ruthenium(II)-rhenium(I) polypyridyl metallomacrocycles. All combinations identified were effective in BRCA-proficient breast cancer cells, including an Olaparib-resistant cell line, and spheroid models. Mechanistic studies indicated that synergy was achieved via DNA-damage enhancement and resultant apoptosis. Combinations showed low cytotoxicity toward non-malignant breast epithelial cells and low acute and developmental toxicity in zebrafish embryos. This work identifies RPC metallomacrocycles as a novel class of agents for cancer combination therapy and provides a proof of concept for the inclusion of metallocompounds within drug synergy screens.
  10. Gan CY, Alkarkhi AF, Easa AM
    J Biosci Bioeng, 2009 Apr;107(4):366-72.
    PMID: 19332294 DOI: 10.1016/j.jbiosc.2008.12.007
    D-optimal design was employed to optimize the mixture of cross-linking agents formulation: microbial transglutaminase (MTGase) and ribose, and the processing parameters (i.e. incubation and heating time) in the mixture in order to obtain combined-cross-linked bovine serum albumin gels that have high gel strength, pH close to neutral and yet medium in browning. Analysis of variance (ANOVA) showed that the contribution of quadratic term to the model over the linear was significant for pH and L* value, whereas linear model was significant for gel strength. Optimization study using response surface methodology (RSM) was performed to the mixture components and process variables and the optimum conditions obtained were: MTGase of 1.34-1.43 g/100 mL, ribose of 1.07-1.16 g/100 mL, incubation time of 5 h at 40 degrees C and heating time of 3 h at 90 degrees C.
    Matched MeSH terms: Ribose/chemistry
  11. Gan CY, Cheng LH, Easa AM
    J Food Sci, 2009 Mar;74(2):C141-6.
    PMID: 19323728 DOI: 10.1111/j.1750-3841.2009.01053.x
    Soy protein isolate (SPI) gels were produced using single cross-linking agents (SCLA) of microbial transglutaminase (MTG) via incubation for 5 or 24 h (SCLA-MTG). When powdered SCLA-MTG gels were heated for 2 h with ribose (R2) (2 g/100 mL), dark brown gels were formed, and these were designated as combined cross-linking agent (CCLA) gels: MTG5(R2) and MTG24(R2). The results showed that the levels of Maillard-derived browning and cross-links of MTG5(R2) and MTG24(R2) gels were significantly (P < 0.05) lower than a control gel produced without MTG (SCLA-R2) even though the percentage of ribose remaining after heating of these gels was similar, indicating that a similar amount of ribose was consumed during heating. epsilon-(gamma-glutamyl)lysine bonds formed during incubation of SPI with MTG may have reduced the free amino group of SPI to take part in the Maillard reaction; nevertheless, ribose took part in the Maillard reaction and initiated the Maillard cross-linkings within the CCLA gels.
    Matched MeSH terms: Ribose/analysis
  12. Sha'fie MSA, Rathakrishnan S, Hazanol IN, Dali MHI, Khayat ME, Ahmad S, et al.
    Antioxidants (Basel), 2020 Dec 09;9(12).
    PMID: 33317056 DOI: 10.3390/antiox9121253
    Microglial cells are the primary immune cell resident in the brain. Growing evidence indicates that microglial cells play a prominent role in alcohol-induced brain pathologies. However, alcohol-induced effects on microglial cells and the underlying mechanisms are not fully understood, and evidence exists to support generation of oxidative stress due to NADPH oxidases (NOX_-mediated production of reactive oxygen species (ROS). Here, we investigated the role of the oxidative stress-sensitive Ca2+-permeable transient receptor potential melastatin-related 2 (TRPM2) channel in ethanol (EtOH)-induced microglial cell death using BV2 microglial cells. Like H2O2, exposure to EtOH induced concentration-dependent cell death, assessed using a propidium iodide assay. H2O2/EtOH-induced cell death was inhibited by treatment with TRPM2 channel inhibitors and also treatment with poly(ADP-ribose) polymerase (PARP) inhibitors, demonstrating the critical role of PARP and the TRPM2 channel in EtOH-induced cell death. Exposure to EtOH, as expected, led to an increase in ROS production, shown using imaging of 2',7'-dichlorofluorescein fluorescence. Consistently, EtOH-induced microglial cell death was suppressed by inhibition of NADPH oxidase (NOX) as well as inhibition of protein kinase C. Taken together, our results suggest that exposure to high doses of ethanol can induce microglial cell death via the NOX/ROS/PARP/TRPM2 signaling pathway, providing novel and potentially important insights into alcohol-induced brain pathologies.
  13. Bhat R, Karim AA
    J Food Sci Technol, 2014 Jul;51(7):1326-33.
    PMID: 24966426 DOI: 10.1007/s13197-012-0652-9
    Developing novel fish gelatin films with better mechanical properties than mammalian gelatin is a challenging but promising endeavor. Studies were undertaken to produce fish gelatin films by combining treatments with different sugars (ribose and lactose) followed 'by' 'and' ultraviolet (UV) radiation, as possible cross-linking agents. Increase in tensile strength and percent elongation at break was recorded, which was more significant in films without sugars that were exposed to UV radiation. Films with added ribose showed decreased solubility after UV treatment and exhibited higher swelling percentage than films with added lactose, which readily dissolved in water. FTIR spectra of all the films showed identical patterns, which indicated no major changes to have occurred in the functional groups as a result of interaction between gelatin, sugars and UV irradiation. The results of this study could be explored for commercial use, depending on industrial needs for either production of edible films or for food packaging purposes.
    Matched MeSH terms: Ribose
  14. Kamarudin F, Gan CY
    Int J Biol Macromol, 2016 Jul;88:280-7.
    PMID: 27044345 DOI: 10.1016/j.ijbiomac.2016.04.003
    Pinto bean pod polysaccharide (PBPP) was successfully extracted with yield of 38.5g/100g and the PBPP gave total carbohydrate and uronic acid contents of 286.2mg maltose equivalent/g and 374.3mgGal/g, respectively. The Mw of PBPP was 270.6kDa with intrinsic viscosity of 0.262dm(3)/g, which composed of mannose (2.5%), galacturonic acid (15.0%), rhamnose (4.0%), glucose (9.0%), galactose (62.2%), xylose (2.9%) and arabinose (4.3%) with trace amount of ribose and fucose. The result suggested that PBPP has a spherical conformation with a highly branched structure. Fourier Transform Infrared analysis showed that PBPP has a similar structure as commercial pectin with an esterification degree of 59.9%, whereas scanning electron microscopy study showed that the crude polysaccharide formed a thin layer of film that was made of multiple micro strands of fibre. PBPP exhibited substantial free radical scavenging activity (7.7%), metal reducing capability (2.04mmol/dm(3)) and α-amylase inhibitory activity (97.6%) at a total amount of 1mg. PBPP also exhibited high water- and oil-holding capacities (3.6g/g and 2.8g/g, respectively). At a low concentration, PBPP exhibited emulsifying activity of 39.6% with stability of 38.6%. Apart from that, PBPP was able to show thickening capability at low concentration (0.005kg/dm(3)).
    Matched MeSH terms: Ribose
  15. Nur Husna SM, Tan HT, Mohamud R, Dyhl-Polk A, Wong KK
    Ther Adv Med Oncol, 2018;10:1758835918808509.
    PMID: 30542378 DOI: 10.1177/1758835918808509
    Breast cancer is the global leading cause of cancer-related death in women and it represents a major health burden worldwide. One of the promising breast cancer therapeutic avenues is through small molecule inhibitors (SMIs) which have undergone rapid progress with successful clinical trials. Recently, three emerging and vital groups of proteins are targeted by SMIs for breast cancer treatment, namely cyclin-dependent kinase 4 and 6 (CDK4/6), poly (adenosine diphosphate-ribose) polymerase (PARP) and phosphoinositide 3-kinase (PI3K). Several of these inhibitors have been approved for the treatment of breast cancer patients or progressed into late-stage clinical trials. Thus, modeling from these successful clinical trials, as well as their limitations, is pivotal for future development and trials of other inhibitors or therapeutic regimens targeting breast cancer patients. In this review, we discuss eight recently approved or novel SMIs against CDK4/6 (palbociclib, ribociclib and abemaciclib), PARP (olaparib, veliparib and talazoparib), and PI3K (buparlisib and alpelisib). The mechanisms of action, series of clinical trials and limitations are described for each inhibitor.
    Matched MeSH terms: Ribose
  16. Seok Fang Oon, Meenakshii Nallappan, Mohd Shazrul Fazry Sa’ariwijaya, Nur Kartinee Kassim, Shamarina Shohaimi, Thiam Tsui Tee, et al.
    MyJurnal
    ABSTRACTS FOR INTERNATIONAL HEALTH AND MEDICAL SCIENCES CONFERENCE 2019 (IHMSC 2019). Accelerating Innovations in Translational and Precision Medicine. Held at Taylor’s University Lakeside Campus, Subang Jaya, Selangor, Malaysia. 8-9th March, 2019
    Introduction: According to the National Health and Morbidity Survey (NHMS) 2015, 47.7% of the Malaysian population are either obese or overweight. The increased obesity prevalence has caused major health problems including cardiovascular diseases and diabetes. Although several anti-obesity drugs have been developed, they are limited due to adverse side effects. Previous studies demonstrated that xanthorrhizol (XNT) reduced the levels of serum free fatty acid and triglyceride in vivo, but the detailed anti-obesity activities and its related mechanisms are yet to be reported. Thus, this study aims to evaluate its abilities to inhibit adipocyte hyperplasia and hypertrophy employing 3T3-L1 adipocytes.
    Methods: Statistical significance was established by one-way ANOVA, where p < 0.05 was considered statistically significant.
    Results: In this study, the IC50 value of XNT (98.3% purity) from Curcuma xanthorrhiza Roxb. in 3T3-L1 adipocytes was 35 ± 0.24 μg/mL. The loss of cell viability was due to 20.01 ± 2.77% of early apoptosis and 24.13 ± 2.03% of late apoptosis. XNT elicited apoptosis via up-regulation of caspase-3 and cleaved PARP-1 protein expression for 4.09-fold and 3.12-fold, respectively. Moreover, XNT decreased adipocyte differentiation for 36.13 ± 3.64% and reduced GPDH activity to 52.26 ± 4.36%. The underlying mechanism was due to impaired expression of PPARγ to 0.36-fold and FAS to 0.38-fold, respectively. On the other hand, XNT increased glycerol release by 45.37 ± 6.08% compared to control. During lipolysis, XNT up-regulated the leptin protein for 2.08-fold but down-regulated the protein level of insulin to 0.36-fold. These results indicated that XNT reduced the volume of adipocytes through modulation of leptin and insulin.
    Conclusion: To conclude, XNT exerted its anti-obesity mechanisms by suppression of adipocyte hyperplasia through induction of apoptosis and inhibition of adipogenesis whilst reduction of adipocyte hypertrophy through stimulation of lipolysis. Thus, XNT could be developed as a potential anti-obesity agent in the future.
  17. Samira, S., Thuan-Chew Tan, T.C., Azhar, M.E.
    MyJurnal
    The effect of ribose-induced Maillard reaction on the physical and mechanical properties of gelatin films was investigated. Bovine gelatin solution (5 g/100 mL) containing glycerol and sorbitol (1:1) was mixed with 20% (R20), 40% ribose (R40), or 40% sucrose (S40) (weight % is based on gelatin dry weight) followed by heating (90ºC, 2 h) and oven drying to produce dried gelatin films. R20 and R40 films were brownish in color with lower light transparency, while CF (control film; without sugars) and S40 were colorless and had higher transparency. Tensile strength and Young Modulus values of the films were in the order; CF > R20 > R40 > S40, while elongation at break was in the order; R40 > S40 > R20 > CF. Water solubility and swelling percentages of the films were in the order; CF > S40 > R20 > R40, indicating the occurrence of insoluble “Maillard complexes” within R20 and R40 films. R20 and R40 films showed maximum light absorption at wavelength of 200 − 350 nm, whilst S40 and CF showed maximum absorbance at 200 − 250 nm. The addition of ribose yielded gelatin films with increased protection against UV light, even though the presence of sugars might had disrupted the inter connection of junction zones and decrease in mechanical properties. Occurrence of the Maillard reaction within R20 and R40 films could be the main reason for differences in physical and mechanical properties of films containing ribose that were formed from heated film-forming solutions.
    Matched MeSH terms: Ribose
  18. Tan, T.C., Abbas, F.M.A., Azhar, M.E.
    MyJurnal
    The addition of ribose to minced chicken or minced pork followed by heating at 95oC yielded minced
    meat with different pH, colour (CIE L*, b*) and absorbance values that can be used as indicators for species differentiation. The higher intensity of the Maillard reaction parameters in minced chicken was due to the higher protein and lysine contents, and the presence of more water-soluble proteins within the minced chicken during heating. Cluster analysis using Maillard reaction parameters showed that the two types of minced meat could be classified into two different groups. A confidence interval (95% confidence) analysis revealed that the absorbance, CIE L* values, and CIE b* values could be used as indicators for differentiation between the two types of minced meat, as the intervals between these Maillard reaction parameters for the two minced meats were far apart.
    Matched MeSH terms: Ribose
  19. Ser HL, Tan LT, Palanisamy UD, Abd Malek SN, Yin WF, Chan KG, et al.
    Front Microbiol, 2016;7:899.
    PMID: 27379040 DOI: 10.3389/fmicb.2016.00899
    A novel strain, Streptomyces antioxidans MUSC 164(T) was recovered from mangrove forest soil located at Tanjung Lumpur, Malaysia. The Gram-positive bacterium forms yellowish-white aerial and brilliant greenish yellow substrate mycelium on ISP 2 agar. A polyphasic approach was used to determine the taxonomy status of strain MUSC 164(T). The strain showed a spectrum of phylogenetic and chemotaxonomic properties consistent with those of the members of the genus Streptomyces. The cell wall peptidoglycan was determined to contain LL-diaminopimelic acid. The predominant menaquinones were identified as MK-9(H6) and MK-9(H8), while the identified polar lipids consisted of aminolipid, diphosphatidylglycerol, glycolipid, hydroxyphosphatidylethanolamine, phospholipid, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol and lipid. The cell wall sugars consist of galactose, glucose and ribose. The predominant cellular fatty acids (>10.0%) were identified as iso-C15: 0 (34.8%) and anteiso-C15: 0(14.0%). Phylogenetic analysis identified that closely related strains for MUSC 164(T) as Streptomyces javensis NBRC 100777(T) (99.6% sequence similarity), Streptomyces yogyakartensis NBRC 100779(T) (99.6%) and Streptomyces violaceusniger NBRC 13459(T) (99.6%). The DNA-DNA relatedness values between MUSC 164(T) and closely related type strains ranged from 23.8 ± 0.3% to 53.1 ± 4.3%. BOX-PCR fingerprints comparison showed that MUSC 164(T) exhibits a unique DNA profile, with DNA G + C content determined to be 71.6 mol%. Based on the polyphasic study of MUSC 164(T), it is concluded that this strain represents a novel species, for which the name Streptomyces antioxidans sp. nov. is proposed. The type strain is MUSC 164(T) (=DSM 101523(T) = MCCC 1K01590(T)). The extract of MUSC 164(T) showed potent antioxidative and neuroprotective activities against hydrogen peroxide. The chemical analysis of the extract revealed that the strain produces pyrazines and phenolic-related compounds that could explain for the observed bioactivities.
    Matched MeSH terms: Ribose
  20. Tee TT, Cheah YH, Hawariah LP
    Anticancer Res, 2007 Sep-Oct;27(5A):3425-30.
    PMID: 17970090
    F16 is a plant-derived pharmacologically active fraction extracted from Eurycoma longifolia Jack. Previously, we have reported that F16 inhibited the proliferation of MCF-7 human breast cancer cells by inducing apoptotic cell death while having some degree of cytoselectivity on a normal human breast cell line, MCF-10A. In this study, we attempted to further elucidate the mode of action of F16. We found that the intrinsic apoptotic pathway was invoked, with the reduction of Bcl-2 protein. Then, executioner caspase-7 was cleaved and activated in response to F16 treatment. Furthermore, apoptosis in the MCF- 7 cells was accompanied by the specific proteolytic cleavage of poly(ADP-ribose) polymerase-1 (PARP-1). Surprisingly, caspase-9 and p53 were unchanged with F16 treatment. We believe that the F16-induced apoptosis in MCF-7 cells occurs independently of caspase-9 and p53. Taken together, these results suggest that F16 from E. longifolia exerts anti-proliferative action and growth inhibition on MCF-7 cells through apoptosis induction and that it may have anticancer properties.
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