Displaying publications 1 - 20 of 58 in total

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  1. Anti-Inflammatory Potential of Ethyl Acetate Fraction of Moringa oleifera in Downregulating the NF-κB Signaling Pathway in Lipopolysaccharide-Stimulated Macrophages
    Arulselvan P, Tan WS, Gothai S, Muniandy K, Fakurazi S, Esa NM, et al.
    Molecules, 2016 Oct 31;21(11).
    PMID: 27809259
    In the present investigation, we prepared four different solvent fractions (chloroform, hexane, butanol, and ethyl acetate) of Moringa oleifera extract to evaluate its anti-inflammatory potential and cellular mechanism of action in lipopolysaccharide (LPS)-induced RAW264.7 cells. Cell cytotoxicity assay suggested that the solvent fractions were not cytotoxic to macrophages at concentrations up to 200 µg/mL. The ethyl acetate fraction suppressed LPS-induced production of nitric oxide and proinflammatory cytokines in macrophages in a concentration-dependent manner and was more effective than the other fractions. Immunoblot observations revealed that the ethyl acetate fraction effectively inhibited the expression of inflammatory mediators including cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor (NF)-κB p65 through suppression of the NF-κB signaling pathway. Furthermore, it upregulated the expression of the inhibitor of κB (IκBα) and blocked the nuclear translocation of NF-κB. These findings indicated that the ethyl acetate fraction of M. oleifera exhibited potent anti-inflammatory activity in LPS-stimulated macrophages via suppression of the NF-κB signaling pathway.
    Matched MeSH terms: Down-Regulation/drug effects*
  2. Fulltext Withaferin A inhibits adipogenesis in 3T3-F442A cell line, improves insulin sensitivity and promotes weight loss in high fat diet-induced obese mice
    Khalilpourfarshbafi M, Devi Murugan D, Abdul Sattar MZ, Sucedaram Y, Abdullah NA
    PLoS One, 2019;14(6):e0218792.
    PMID: 31226166 DOI: 10.1371/journal.pone.0218792
    The increased prevalence of obesity and associated insulin resistance calls for effective therapeutic treatment of metabolic diseases. The current PPARγ-targeting antidiabetic drugs have undesirable side effects. The present study investigated the anti-diabetic and anti-obesity effects of withaferin A (WFA) in diet-induced obese (DIO) C57BL/6J mice and also the anti-adipogenic effect of WFA in differentiating 3T3- F442A cells. DIO mice were treated with WFA (6 mg/kg) or rosiglitazone (10 mg/kg) for 8 weeks. At the end of the treatment period, metabolic profile, liver function and inflammatory parameters were obtained. Expression of selective genes controlling insulin signaling, inflammation, adipogenesis, energy expenditure and PPARγ phosphorylation-regulated genes in epididymal fats were analyzed. Furthermore, the anti-adipogenic effect of WFA was evaluated in 3T3- F442A cell line. WFA treatment prevented weight gain without affecting food or caloric intake in DIO mice. WFA-treated group also exhibited lower epididymal and mesenteric fat pad mass, an improvement in lipid profile and hepatic steatosis and a reduction in serum inflammatory cytokines. Insulin resistance was reduced as shown by an improvement in glucose and insulin tolerance and serum adiponectin. WFA treatment upregulated selective insulin signaling (insr, irs1, slc2a4 and pi3k) and PPARγ phosphorylation-regulated (car3, selenbp1, aplp2, txnip, and adipoq) genes, downregulated inflammatory (tnf-α and il-6) genes and altered energy expenditure controlling (tph2 and adrb3) genes. In 3T3- F442A cell line, withaferin A inhibited adipogenesis as indicated by a decrease in lipid accumulation in differentiating adipocytes and protein expression of PPARγ and C/EBPα. The effect of rosiglitazone on physiological and lipid profiles, insulin resistance, some genes expression and differentiating adipocytes were markedly different. Our data suggest that WFA is a promising therapeutic agent for both diabetes and obesity.
    Matched MeSH terms: Down-Regulation/drug effects
  3. Arjunolic acid downregulates elevated blood sugar and pro-inflammatory cytokines in streptozotocin (STZ)-nicotinamide induced type 2 diabetic rats
    Aamir K, Khan HU, Hossain CF, Afrin MR, Jusuf PR, Waheed I, et al.
    Life Sci, 2022 Jan 15;289:120232.
    PMID: 34919901 DOI: 10.1016/j.lfs.2021.120232
    BACKGROUND: Type 2 diabetes mellitus (T2DM) is a worldwide health issue primarily due to failure of pancreatic β-cells to release sufficient insulin.

    PURPOSE: The present work aimed to assess the antidiabetic potential of arjunolic acid (AA) isolated from Terminalia arjuna in type 2 diabetic rats.

    STUDY DESIGN: After extraction, isolation and purification, AA was orally administered to type 2 diabetic Sprague Dawley rats to investigate antidiabetic effect of AA.

    METHOD: T2DM was induced via single intraperitoneal injection of streptozotocin-nicotinamide (STZ-NIC) in adult male rats. After 10 days, fasting and random blood glucose (FBG and RBG), body weight (BW), food and water intake, serum C-peptide, insulin and glycated hemoglobin (HbA1c) was measured to confirm T2DM development. Dose dependent effects of orally administered AA (25 and 50 mg/kg/day) for 4 weeks was investigated by measuring BW variation, fasting and postprandial hyperglycemia, oral glucose tolerance test (OGTT), and levels of serum HbA1c, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), serum and pancreatic C-peptide, insulin, growth differentiation factor 15 (GDF-15), serum and pancreatic inflammatory cytokines.

    RESULTS: The oral administration of AA in preclinical model of T2DM significantly normalized FBG and RBG, restored BW, controlled polyphagia, polydipsia and glucose tolerance. In addition, AA notably reduced serum HbA1c, TC, TG, LDL with non-significant increase in HDL. On the other hand, significant increase in serum and pancreatic C-peptide and insulin was observed with AA treatment, while serum and pancreatic GDF-15 were non-significantly altered in AA treated diabetic rats. Moreover, AA showed dose dependent reduction in serum and pancreatic proinflammatory cytokines including TNF-α, IL-1β and IL-6.

    CONCLUSION: For the first time our findings highlighted AA as a potential candidate in type 2 diabetic conditions.

    Matched MeSH terms: Down-Regulation/drug effects*
  4. Expression profile of genes modulated by Aloe emodin in human U87 glioblastoma cells
    Haris K, Ismail S, Idris Z, Abdullah JM, Yusoff AA
    Asian Pac J Cancer Prev, 2014;15(11):4499-505.
    PMID: 24969876
    Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with 58.6 μg/ml for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.
    Matched MeSH terms: Down-Regulation/drug effects
  5. Fulltext Capgermacrenes A and B, Bioactive Secondary Metabolites from a Bornean Soft Coral, Capnella sp
    Phan CS, Ng SY, Kim EA, Jeon YJ, Palaniveloo K, Vairappan CS
    Mar Drugs, 2015 May;13(5):3103-15.
    PMID: 25996100 DOI: 10.3390/md13053103
    Two new bicyclogermacrenes, capgermacrenes A (1) and B (2), were isolated with two known compounds, palustrol (3) and litseagermacrane (4), from a population of Bornean soft coral Capnella sp. The structures of these metabolites were elucidated based on spectroscopic data. Compound 1 was found to inhibit the accumulation of the LPS-induced pro-inflammatory IL-1b and NO production by down-regulating the expression of iNOS protein in RAW 264.7 macrophages.
    Matched MeSH terms: Down-Regulation/drug effects
  6. Anti-melanin deposition activity of ceramicines from Chisocheton ceramicus
    Iijima C, Wong CP, Nugroho AE, Sotozono Y, Someya S, Hirasawa Y, et al.
    J Nat Med, 2016 Oct;70(4):702-7.
    PMID: 27357963 DOI: 10.1007/s11418-016-1016-y
    The ceramicines, a series of limonoids from Chisocheton ceramicus (Meliaceae), were evaluated for anti-melanin deposition activity on α-melanocyte stimulating hormone (α-MSH) and 3-isobutyl-1-methylxanthine (IBMX)-treated B16-F10 melanoma cell, and several ceramicines were found to be active. The structure-activity relationship of ceramicines as anti-melanin deposition inhibitors was deduced. Furthermore, the mechanism of anti-melanin deposition activity of ceramicine B, a major constituent of C. ceramicus that showed potent anti-melanin deposition activity, was investigated. Tyrosinase enzymatic activity and tyrosinase mRNA expression were not affected by ceramicine B. The anti-melanin deposition activity of ceramicine B was shown to be related to the downregulation of tyrosinase protein expression. These results suggest that ceramicines have potential to be used as depigmentation agents.
    Matched MeSH terms: Down-Regulation/drug effects
  7. Adenine derivatives invert high glucose-induced thioredoxin-interacting protein overexpression
    Zhong L, Liu Q, Ting YS, Thien VY, Binti Kalong NS, Yang D, et al.
    Chem Biol Drug Des, 2018 12;92(6):1998-2008.
    PMID: 30043441 DOI: 10.1111/cbdd.13371
    Overexpression of thioredoxin-interacting protein (TXNIP) is associated with reduced insulin sensitivity and β-cell apoptosis. We have previously shown that W2476 inhibited high glucose-induced TXNIP expression at both mRNA and protein levels in INS-1E cells. In this study, we describe structural modification and optimization of W2476 leading to three more active derivatives, 8d, 8g, and 9h, capable of suppressing TXNIP expression in BG73 and INS-1E cells, increasing insulin production, and reducing high glucose-induced apoptosis in INS-1E cells.
    Matched MeSH terms: Down-Regulation/drug effects*
  8. Profiling of gene expression in methicillin-resistant Staphylococcus aureus in response to cyclo-(L-Val-L-Pro) and chloramphenicol isolated from Streptomyces sp., SUK 25 reveals gene downregulation in multiple biological targets
    Zin NM, Al-Shaibani MM, Jalil J, Sukri A, Al-Maleki AR, Sidik NM
    Arch Microbiol, 2020 Oct;202(8):2083-2092.
    PMID: 32494868 DOI: 10.1007/s00203-020-01896-x
    Chloramphenicol (CAP) and cyclo-(L-Val-L-Pro) were previously isolated from Streptomyces sp., SUK 25 which exhibited a high potency against methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to profile gene expression of MRSA treated with CAP and cyclo-(L-Val-L-Pro) compounds using DNA microarray. Treatment of MRSA with CAP resulted in upregulation of genes involved in protein synthesis, suggesting the coping mechanism of MRSA due to the inhibition of protein synthesis effect from CAP. Most upregulated genes in cyclo-(L-Val-L-Pro) were putative genes with unknown functions. Interestingly, genes encoding ribosomal proteins, cell membrane synthesis, DNA metabolism, citric acid cycle and virulence were downregulated in MRSA treated with cyclo-(L-Val-L-Pro) compound, suggesting the efficacy of this compound in targeting multiple biological pathways. Contrary to CAP, with only a single target, cyclo-(L-Val-L-Pro) isolated from this study had multiple antimicrobial targets that can delay antibiotic resistance and hence is a potential antimicrobial agent of MRSA.
    Matched MeSH terms: Down-Regulation/drug effects*
  9. Fulltext Bee bread mitigates downregulation of steroidogenic genes, decreased spermatogenesis, and epididymal oxidative stress in male rats fed with high-fat diet
    Suleiman JB, Abu Bakar AB, Noor MM, Nna VU, Othman ZA, Zakaria Z, et al.
    Am J Physiol Endocrinol Metab, 2021 Sep 01;321(3):E351-E366.
    PMID: 34229480 DOI: 10.1152/ajpendo.00093.2021
    The pituitary-gonadal axis plays an important role in steroidogenesis and spermatogenesis, and by extension, fertility. The aim of this study was to investigate the protective role of bee bread, a natural bee product, against obesity-induced decreases in steroidogenesis and spermatogenesis. Thirty-two adult male Sprague-Dawley rats weighing between 200 and 300 g were divided into four groups (n = 8/group), namely: normal control (NC), high-fat diet (HFD), HFD plus bee bread administered concurrently for 12 wk (HFD + B), HFD plus orlistat administered concurrently for 12 wk (HFD + O) groups. Bee bread (0.5 g/kg) or orlistat (10 mg/kg/day) was suspended in distilled water and given by oral gavage daily for 12 wk. Levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and adiponectin, as well as sperm count, motility, viability, normal morphology, and epididymal antioxidants decreased, whereas levels of leptin, malondialdehyde, and sperm nDNA fragmentation increased significantly in the HFD group relative to the NC group. There were significant decreases in the testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme, 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD in the testes of the HFD group. Furthermore, mount, intromission and ejaculatory latencies increased, and penile cGMP level decreased significantly in the HFD group. Supplementation with bee bread significantly reduced leptin level and increased adiponectin level, enhanced sperm parameters and reduced sperm nDNA fragmentation, upregulated the levels of steroidogenic genes and proteins in HFD-induced obese male rats. Bee bread improved steroidogenesis and spermatogenesis by upregulating steroidogenic genes. Therefore, bee bread may be considered as a potential supplementation to protect against infertility in overweight men or men with obesity.NEW & NOTEWORTHY The high-fat diet utilized in the present study induced obesity in the male rats. Bee bread supplementation mitigated impaired steroidogenesis, spermatogenesis, mating behavior, and fertility potential by counteracting the downregulation of steroidogenic genes, thus increasing testosterone levels and suppressing epididymal oxidative stress. These benefits may be due to the abundance of phenolic and flavonoid compounds in bee bread.
    Matched MeSH terms: Down-Regulation/drug effects
  10. Fulltext Downregulation of immunological mediators in 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions by hydrocortisone-loaded chitosan nanoparticles
    Hussain Z, Katas H, Mohd Amin MC, Kumolosasi E, Sahudin S
    Int J Nanomedicine, 2014;9:5143-56.
    PMID: 25395851 DOI: 10.2147/IJN.S71543
    Atopic dermatitis is a chronic, noncontiguous, and exudative disorder accompanied by perivascular infiltration of immune mediators, including T-helper (Type 1 helper/Type 2 helper) cells, mast cells, and immunoglobulin E. The current study explores the immunomodulatory and histological effects of nanoparticle (NP)-based transcutaneous delivery of hydrocortisone (HC).
    Matched MeSH terms: Down-Regulation/drug effects
  11. 2-Methoxy-1,4-Naphthoquinone (MNQ) suppresses the invasion and migration of a human metastatic breast cancer cell line (MDA-MB-231)
    Liew K, Yong PV, Lim YM, Navaratnam V, Ho AS
    Toxicol In Vitro, 2014 Apr;28(3):335-9.
    PMID: 24291160 DOI: 10.1016/j.tiv.2013.11.008
    Metastasis contributes to the escalating mortality rate among cancer patients worldwide. The search for novel and more effective anti-metastatic agent is crucial owing to the lack of anticancer drugs that can successfully combat metastasis. Hence, this study aims to examine the effects of 2-Methoxy-1,4-Naphthoquinone (MNQ) towards the metastasis of MDA-MB-231 cells. In invasion assays, the number of cells permeating across a Matrigel barrier was found to be decreased in a dose-dependent manner upon treatment with MNQ (0-7.5 μM). In wound-healing migration assays, MNQ exhibited dose-dependent inhibition of cell migration in which significant reduction in the zone of closure was observed as compared to untreated controls. Furthermore, the proteolytic activity of a pivotal metastatic mediator, matrix metalloproteinase-9 (MMP-9) was also downregulated by MNQ as determined by gelatin zymography. This study reports for the first time, the ability of MNQ to inhibit the invasion and migration characteristics of a highly metastatic MDA-MB-231 cancer cell line.
    Matched MeSH terms: Down-Regulation/drug effects
  12. Fulltext Effects of germinated brown rice and its bioactive compounds on the expression of the peroxisome proliferator-activated receptor gamma gene
    Imam MU, Ismail M, Ithnin H, Tubesha Z, Omar AR
    Nutrients, 2013 Feb;5(2):468-77.
    PMID: 23389305 DOI: 10.3390/nu5020468
    Dysregulated metabolism is implicated in obesity and other disease conditions like type 2 diabetes mellitus and cardiovascular diseases, which are linked to abnormalities of peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ has been the focus of much research aimed at managing these diseases. Also, germinated brown rice (GBR) is known to possess antidiabetic, antiobesity and hypocholesterolemic effects. We hypothesized that GBR bioactive compounds may mediate some of the improvements in metabolic indices through PPARγ modulation. Cultured HEP-G2 cells were treated with 50 ppm and 100 ppm of extracts from GBR (GABA, ASG and oryzanol) after determination of cell viabilities using MTT assays. Results showed that all extracts upregulated the expression of the PPARγ. However, combination of all three extracts showed downregulation of the gene, suggesting that, in combination, the effects of these bioactives differ from their individual effects likely mediated through competitive inhibition of the gene. Upregulation of the gene may have therapeutic potential in diabetes mellitus and cardiovascular diseases, while its downregulation likely contributes to GBR's antiobesity effects. These potentials are worth studying further.
    Matched MeSH terms: Down-Regulation/drug effects
  13. Fulltext The Curcumin Analogue 1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one Induces Apoptosis and Downregulates E6 and E7 Oncogene Expression in HPV16 and HPV18-Infected Cervical Cancer Cells
    Paulraj F, Abas F, Lajis NH, Othman I, Hassan SS, Naidu R
    Molecules, 2015;20(7):11830-60.
    PMID: 26132907 DOI: 10.3390/molecules200711830
    In an effort to study curcumin analogues as an alternative to improve the therapeutic efficacy of curcumin, we screened the cytotoxic potential of four diarylpentanoids using the HeLa and CaSki cervical cancer cell lines. Determination of their EC50 values indicated relatively higher potency of 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one (MS17, 1.03 ± 0.5 μM; 2.6 ± 0.9 μM) and 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13, 2.8 ± 0.4; 6.7 ± 2.4 μM) in CaSki and HeLa, respectively, with significantly greater growth inhibition at 48 and 72 h of treatment compared to the other analogues or curcumin. Based on cytotoxic and anti-proliferative activity, MS17 was selected for comprehensive apoptotic studies. At 24 h of treatment, fluorescence microscopy detected that MS17-exposed cells exhibited significant morphological changes consistent with apoptosis, corroborated by an increase in nucleosomal enrichment due to DNA fragmentation in HeLa and CaSki cells and activation of caspase-3 activity in CaSki cells. Quantitative real-time PCR also detected significant down-regulation of HPV18- and HPV16-associated E6 and E7 oncogene expression following treatment. The overall data suggests that MS17 treatment has cytotoxic, anti-proliferative and apoptosis-inducing potential in HPV-positive cervical cancer cells. Furthermore, its role in down-regulation of HPV-associated oncogenes responsible for cancer progression merits further investigation into its chemotherapeutic role for cervical cancer.
    Matched MeSH terms: Down-Regulation/drug effects*
  14. Pro-atherogenic proteoglycanase ADAMTS-1 is down-regulated by lauric acid through PI3K and JNK signaling pathways in THP-1 derived macrophages
    Ong MH, Wong HK, Tengku-Muhammad TS, Choo QC, Chew CH
    Mol Biol Rep, 2019 Jun;46(3):2631-2641.
    PMID: 30989556 DOI: 10.1007/s11033-019-04661-6
    The prevalence of atherosclerosis has increased significantly in the recent years due to sedentary lifestyle and high-fat diet. However, the association between saturated fat intake and the increased risk for atherosclerotic cardiovascular diseases remains heavily debated. Lauric acid belongs to the saturated fatty acid group and its unique medium chain fatty acid properties are proven to be beneficial to humans in many ways. Thus, the aim of this project is to investigate the effect of lauric acid on the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes-ADAMTS-1, ADAMTS-4, and ADAMTS-5-in macrophages. These genes encode for proteases that participate in the extracellular matrix remodeling and they play important roles in the vulnerability of atherosclerotic plaque. Here, we show that the treatment of 20 µM of lauric acid successfully reduced both transcriptional and translational expressions of these genes in THP-1 differentiated macrophages after 24-h incubation. Further cell signaling experiments using a panel of kinase inhibitors and phosphorylated antibodies proved that lauric acid down-regulated ADAMTS-1 by reducing the activation of PI3K and JNK at Tyr458 and Tyr185, respectively. Finally, JNK1 siRNA knockdown assay confirmed that ADAMTS-1 was regulated through JNK pathway, and lauric acid interfered with this pathway to down-regulate ADAMTS-1 expression. Although preliminary, this present study indicates that lauric acid has the potential to stabilize atherosclerotic plaque and may prevent thrombosis by interfering with the ADAMTS-1 expression through PI3K/JNK pathways.
    Matched MeSH terms: Down-Regulation/drug effects
  15. Inhibition of lysosomal vacuolar proton pump down-regulates cellular acidification and enhances E. coli bactofection efficiency
    Akinsola RO, Lee CW, Sim EUH, Narayanan K
    Anal Biochem, 2021 03 01;616:114088.
    PMID: 33358938 DOI: 10.1016/j.ab.2020.114088
    Endosomal escape is considered a crucial barrier that needs to be overcome by integrin-mediated E. coli for gene delivery into mammalian cells. Bafilomycin, a potent inhibitor of the H+ proton pump commonly employed to lower endosomal pH, was evaluated as part of the E. coli protocol during delivery. We found an increase in green fluorescent protein expression up 6.9, 3.2, 5.0, 2.8, and 4.5 fold in HeLa, HEK-293, A549, HT1080, and MCF-7 respectively, compared to untreated cells. Our result showed for the first time that Inhibition of lysosomal V-ATPase enhances E. coli efficiency.
    Matched MeSH terms: Down-Regulation/drug effects
  16. Fulltext RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways
    Jiang L, Hindmarch CC, Rogers M, Campbell C, Waterfall C, Coghill J, et al.
    Sci Rep, 2016 10 24;6:35671.
    PMID: 27774996 DOI: 10.1038/srep35671
    Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or 'podocytes', the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells. The upregulated genes are of functional relevance to cytoskeleton-related processes, whereas the downregulated genes mostly encode pro-inflammatory cytokines and growth factors. We observed a tendency for dexamethasone-upregulated genes to be downregulated in MCN patients. Integrative analysis revealed gene networks composed of critical signaling pathways that are likely targeted by dexamethasone in podocytes.
    Matched MeSH terms: Down-Regulation/drug effects
  17. Fulltext Bromelain Enhances the Anti-tumor Effects of Cisplatin on 4T1 Breast Tumor Model In Vivo
    Mohamad NE, Abu N, Yeap SK, Alitheen NB
    Integr Cancer Ther, 2019 11 23;18:1534735419880258.
    PMID: 31752555 DOI: 10.1177/1534735419880258
    Background: This study aimed to evaluate the antitumor enhancing effect of bromelain consumption on 4T1-challenged mice treated with cisplatin. Methods: Mice challenged with 4T1 triple-negative breast cancer cells received water, bromelain, cisplatin, or bromelain + cisplatin treatment for 28 days. Tumor size was measured, and lung metastasis was evaluated by clonogenic assay. Expression of tumor inflammatory genes of the harvested tumor was quantified by polymerase chain reaction array and ELISA (enzyme-linked immunosorbent assay). Results: All treatments significantly reduced the size of tumor and lung metastasis, with combination treatment showing the best effect. Also, bromelain alone and combination treatment showed downregulation of the expression of tumor inflammatory genes (Gremlin [GREM1], interleukin 1β [IL-1β], interleukin-4 [IL-4], nuclear factor κB subunit 1 [NFκB1], and prostaglandin-endoperoxide synthase 2 [PTGS2]), tumor nitric oxide level, and serum IL-1β, and IL-4 levels. On the other hand, cisplatin treatment increased the expression of selected inflammatory markers. Conclusion: This study suggests that bromelain treatment could potentiate the antitumor effect of cisplatin on triple-negative breast cancer 4T1 cells through modulating the tumor environmental inflammation.
    Matched MeSH terms: Down-Regulation/drug effects
  18. Methadone hydrochloride and leukemia cells: Effects on cell viability, DNA fragmentation and apoptotic proteins expression level
    Kua VMD, Rasul A, Sreenivasan S, Rasool B, Younis T, Lai NS
    Pak J Pharm Sci, 2019 Jul;32(4(Supplementary)):1797-1803.
    PMID: 31680075
    Leukemia is a type of blood cancer where abnormal and immature leucocytes are produced in the bone marrow. Methadone hydrochloride is a man-made drug that is commonly used in the maintenance treatment for drug addiction. The objective of this research was to determine the cytotoxic activity and apoptotic effects of methadone hydrochloride treatment towards two leukemia cell lines which are CCRF-CEM and HL-60. CCRF-CEM and HL-60 cells were treated with methadone hydrochloride for 24 and 48 hours to determine the cytotoxic activity. IC50 at 24 hours obtained for CCRF-CEM was 121.6μmol/L while IC50 for HL-60 cells was 97.18μmol/L. Result obtained from DNA fragmentation assay showed no characteristic DNA ladder pattern in CCRF-CEM leukemia cells treated with methadone hydrochloride. Characteristics DNA ladder pattern was observed in methadone hydrochloride treated HL-60 cells. Formation of comets was seen in methadone hydrochloride treated CCRF-CEM and HL-60 cells with varying degree of DNA damage. The comets formed by methadone hydrochloride treated HL-60 cells were more prominent as compared to methadone-treated CCRF-CEM cells. The expression of apoptotic-related proteins in methadone-treated CCRF-CEM and HL-60 cells were checked by incubating the cell lysate with Raybio® Human Apoptosis Antibody Array. Significant alterations in expression level of apoptosis-related proteins in methadone hydrochloride treated CCRF-CEM cells were found involving upregulation of caspase-8 expression and downregulation of survivin expression. Methadone hydrochloride induced apoptosis in HL-60 cells involved upregulation of Bid and caspase-8 expression and downregulation of Bcl-2, p21 and survivin expression.
    Matched MeSH terms: Down-Regulation/drug effects
  19. Fulltext Progesterone downregulates oestrogen-induced expression of CFTR and SLC26A6 proteins and mRNA in rats' uteri
    Gholami K, Muniandy S, Salleh N
    J Biomed Biotechnol, 2012;2012:596084.
    PMID: 23226939 DOI: 10.1155/2012/596084
    Under progesterone (P) dominance, fluid loss assists uterine closure which is associated with pH reduction. We hypothesize that P inhibits uterine fluid secretion and HCO3⁻ transport.
    Matched MeSH terms: Down-Regulation/drug effects
  20. Fulltext Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase
    Abrahim NN, Kanthimathi MS, Abdul-Aziz A
    BMC Complement Altern Med, 2012 Nov 15;12:220.
    PMID: 23153283 DOI: 10.1186/1472-6882-12-220
    BACKGROUND: Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7.

    METHODS: The leaves of P. betle were extracted with solvents of varying polarities (water, methanol, ethyl acetate and hexane) and their phenolic and flavonoid content were determined using colorimetric assays. Phenolic composition was characterized using HPLC. Antioxidant activities were measured using FRAP, DPPH, superoxide anion, nitric oxide and hyroxyl radical scavenging assays. Biological activities of the extracts were analysed using MTT assay and antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase) assays in MCF-7 cells.

    RESULTS: Overall, the ethyl acetate extract showed the highest ferric reducing activity and radical scavenging activities against DPPH, superoxide anion and nitric oxide radicals. This extract also contained the highest phenolic content implying the potential contribution of phenolics towards the antioxidant activities. HPLC analyses revealed the presence of catechin, morin and quercetin in the leaves. The ethyl acetate extract also showed the highest inhibitory effect against the proliferation of MCF-7 cells (IC50=65 μg/ml). Treatment of MCF-7 cells with the plant extract increased activities of catalase and superoxide dismutase.

    CONCLUSIONS: Ethyl acetate is the optimal solvent for the extraction of compounds with antioxidant and anti-proliferative activities. The increased activities of catalase and superoxide dismutase in the treated cells could alter the antioxidant defense system, potentially contributing towards the anti-proliferative effect. There is great potential for the ethyl acetate extract of P. betle leaf as a source of natural antioxidants and to be developed as therapeutics in cancer treatment.

    Matched MeSH terms: Down-Regulation/drug effects
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