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Intron retention is among six unreported AGL mutations identified in Malaysian GSD III patients

Abdullah IS, Teh SH, Khaidizar FD, Ngu LH, Keng WT, Yap S, et al.

Genes Genomics, 2019 08;41(8):885-893.
PMID: 31028654 DOI: 10.1007/s13258-019-00815-9

BACKGROUND: Glycogen storage disease type III is an autosomal recessive disorder that is caused by deficiencies of the glycogen debranching enzyme. Mutations within the AGL gene have been found to be heterogeneous, with some common mutations being reported in certain populations. The mutation spectrum of AGL gene in the multi-ethnic Malaysian population is still unknown.
OBJECTIVE: The present study seeks to determine the mutation spectrum of the AGL gene in Malaysian population.
METHODS: A total of eleven patients (eight Malay, two Chinese and one Bajau) were investigated. Genomic DNA was extracted and subsequently the AGL gene was amplified using specific primers and sequenced. Mutations found were screened in 150 healthy control samples either by restriction enzyme digestion assay or TaqMan® SNP Genotyping assay.
RESULTS: We identified six unreported mutations (c.1423+1G>T, c.2914_2915delAA, c.3814_3815delAG, c.4333T>G, c.4490G>A, c.4531_4534delTGTC) along with three previously reported mutations (c.99C>T, c.1783C>T, c.2681+1G>A). One of the six unreported mutation causes abnormal splicing and results in retention of intron 12 of the mature transcript, while another is a termination read-through. One of the reported mutation c.2681+1G>A was recurrently found in the Malay patients (n = 7 alleles; 31.8%).
CONCLUSION: The mutation spectrum of the AGL gene in Malaysian patients has shown considerable heterogeneity, and all unreported mutations were absent in all 150 healthy control samples tested.

Matched MeSH terms: Glycogen Debranching Enzyme System/genetics*; Glycogen Debranching Enzyme System/metabolism; Glycogen Storage Disease Type III/genetics*; Glycogen Storage Disease Type III/pathology
Cellular and hormonal control in glycogen metabolism--recent advances

Thambyrajah V, Karunairatnam MC

Med J Malaya, 1972 Sep;27(1):33-9.
PMID: 4345646
Matched MeSH terms: Glycogen/biosynthesis; Glycogen/metabolism*; Glycogen Synthase/metabolism
Environmental changes affecting physiological responses and growth of hybrid grouper - The interactive impact of low pH and temperature

Thalib YA, Razali RS, Mohamad S, Zainuddin R', Rahmah S, Ghaffar MA, et al.

Environ Pollut, 2021 Feb 15;271:116375.
PMID: 33422747 DOI: 10.1016/j.envpol.2020.116375

Rising of temperature in conjunction with acidification due to the anthropogenic climates has tremendously affected all aquatic life. Small changes in the surrounding environment could lead to physiological constraint in the individual. Therefore, this study was designed to investigate the effects of warm water temperature (32 °C) and low pH (pH 6) on physiological responses and growth of hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) juveniles for 25 days. Growth performance was significantly affected under warm water temperature and low-pH conditions. Surprisingly, the positive effect on growth was observed under the interactive effects of warm water and low pH exposure. Hybrid grouper exposed to the interactive stressor of warm temperature and low pH exhibited higher living cost, where HSI content was greatly depleted to about 2.3-folds than in normal circumstances. Overall, challenge to warm temperature and low pH induced protein mobilization as an energy source followed by glycogen and lipid to support basal metabolic needs.

Matched MeSH terms: Glycogen
A review of natural polysaccharides for drug delivery applications: Special focus on cellulose, starch and glycogen

Gopinath V, Saravanan S, Al-Maleki AR, Ramesh M, Vadivelu J

Biomed Pharmacother, 2018 Nov;107:96-108.
PMID: 30086465 DOI: 10.1016/j.biopha.2018.07.136

Natural polysaccharides are renewable with a high degree of biocompatibility, biodegradability, and ability to mimic the natural extracellular matrix (ECM) microenvironment. Comprehensive investigations of polysaccharides are essential for our fundamental understanding of exploiting its potential as bio-composite, nano-conjugate and in pharmaceutical sectors. Polysaccharides are considered to be superior to other polymers, for its ease in tailoring, bio-compatibility, bio-activity, homogeneity and bio-adhesive properties. The main focus of this review is to spotlight the new advancements and challenges concerned with surface modification, binding domains, biological interaction with the conjugate including stability, polydispersity, and biodegradability. In this review, we have limited our survey to three essential polysaccharides including cellulose, starch, and glycogen that are sourced from plants, microbes, and animals respectively are reviewed. We also present the polysaccharides which have been extensively modified with the various types of conjugates for combating last-ditch pharmaceutical challenges.

Matched MeSH terms: Glycogen/pharmacology*
Effects of insulin on the structure and metabolism of glucogen in chemically-induced diabetic rats

Kwan TK, Thambyrajah V

Med J Malaysia, 1978 Dec;33(2):178-83.
PMID: 755172
Matched MeSH terms: Glycogen/biosynthesis; Glycogen/metabolism*
Computational Analysis of Protein-Protein Interactions in Motile T-Cells

Kumar S, Fazil MHUT, Ahmad K, Tripathy M, Rajapakse JC, Verma NK

Methods Mol Biol, 2019;1930:149-156.
PMID: 30610609 DOI: 10.1007/978-1-4939-9036-8_18

Analysis of protein-protein interactions is important for better understanding of molecular mechanisms involved in immune regulation and has potential for elaborating avenues for drug discovery targeting T-cell motility. Currently, only a small fraction of protein-protein interactions have been characterized in T-lymphocytes although there are several detection methods available. In this regard, computational approaches garner importance, with the continued explosion of genomic and proteomic data, for handling protein modeling and protein-protein interactions in large scale. Here, we describe a computational method to identify protein-protein interactions based on in silico protein design.

Matched MeSH terms: Glycogen Synthase Kinase 3 beta/metabolism; Glycogen Synthase Kinase 3 beta/chemistry
Glycogen synthase kinase-3 beta (GSK-3β) signaling: Implications for Parkinson's disease

Golpich M, Amini E, Hemmati F, Ibrahim NM, Rahmani B, Mohamed Z, et al.

Pharmacol Res, 2015 Jul;97:16-26.
PMID: 25829335 DOI: 10.1016/j.phrs.2015.03.010

Glycogen synthase kinase 3 (GSK-3) dysregulation plays an important role in the pathogenesis of numerous disorders, affecting the central nervous system (CNS) encompassing both neuroinflammation and neurodegenerative diseases. Several lines of evidence have illustrated a key role of the GSK-3 and its cellular and molecular signaling cascades in the control of neuroinflammation. Glycogen synthase kinase 3 beta (GSK-3β), one of the GSK-3 isomers, plays a major role in neuronal apoptosis and its inhibition decreases expression of alpha-Synuclein (α-Synuclein), which make this kinase an attractive therapeutic target for neurodegenerative disorders. Parkinson's disease (PD) is a chronic neurodegenerative movement disorder characterized by the progressive and massive loss of dopaminergic neurons by neuronal apoptosis in the substantia nigra pars compacta and depletion of dopamine in the striatum, which lead to pathological and clinical abnormalities. Thus, understanding the role of GSK-3β in PD will enhance our knowledge of the basic mechanisms underlying the pathogenesis of this disorder and facilitate the identification of new therapeutic avenues. In recent years, GSK-3β has been shown to play essential roles in modulating a variety of cellular functions, which have prompted efforts to develop GSK-3β inhibitors as therapeutics. In this review, we summarize GSK-3 signaling pathways and its association with neuroinflammation. Moreover, we highlight the interaction between GSK-3β and several cellular processes involved in the pathogenesis of PD, including the accumulation of α-Synuclein aggregates, oxidative stress and mitochondrial dysfunction. Finally, we discuss about GSK-3β inhibitors as a potential therapeutic strategy in PD.

Matched MeSH terms: Glycogen Synthase Kinase 3/antagonists & inhibitors; Glycogen Synthase Kinase 3/drug effects; Glycogen Synthase Kinase 3/physiology*
Juvenile acid maltase deficiency

Loi, H.D.K., Wong, K.T., Choo, K.E.

Malaysian Journal of Paediatrics and Child Health, 2005;14(1):58-63.
MyJurnal

An eight-year-old Chinese girl presented with a slowly progressive generalized muscle weakness and wasting, complicated by respiratory failure. She had many hospital admissions requiring ventilator support. Eventually tracheostomy tube was inserted. Initial investigations failed to elicit a diagnosis but a muscle biopsy and histological study confirmed the diagnosis of juvenile acid maltase deficiency.

Matched MeSH terms: Glycogen Storage Disease Type II
Efficacy of methylprednisolone on T-2 toxin-induced cardiotoxicity in vivo: A pathohistological study

Jaćević V, Wu Q, Nepovimova E, Kuča K

Environ Toxicol Pharmacol, 2019 Oct;71:103221.
PMID: 31365892 DOI: 10.1016/j.etap.2019.103221

Our aim was to compare the protective efficacy of two different formulations of methylprednisolone in T-2 toxin-induced cardiomyopathy. Methylprednisolone (soluble form, Lemod-solu® and/or depot form, Lemod-depo®, a total single dose of 40 mg/kg im) was given immediately after T-2 toxin (1 LD50 0.23 mg/kg sc). The myocardial tissue samples were examinated by using histopathology, semiquantitative and imaging analyses on day 1, 7, 14, 21, 28 and 60 of the study. Therapeutic application of Lemod-solu® significantly decreased the intensity of myocardial degeneration and haemorrhages, distribution of glycogen granules in the endo- and perimysium, a total number of mast cells and the degree of their degranulation was in correlation with the reversible heart structural lesions (p 

Matched MeSH terms: Glycogen
Kinetic and stoichiometric characterization for efficient enhanced biological phosphorus removal (EBPR) process at high temperatures

Liau KF, Shoji T, Ong YH, Chua AS, Yeoh HK, Ho PY

Bioprocess Biosyst Eng, 2015 Apr;38(4):729-37.
PMID: 25381606 DOI: 10.1007/s00449-014-1313-3

A recently reported stable and efficient EBPR system at high temperatures around 30 °C has led to characterization of kinetic and stoichiometric parameters of the Activated Sludge Model no. 2d (ASM2d). Firstly, suitable model parameters were selected by identifiability analysis. Next, the model was calibrated and validated. ASM2d was found to represent the processes well at 28 and 32 °C except in polyhyroxyalkanoate (PHA) accumulation of the latter. The values of the kinetic parameters for PHA storage (q PHA), polyphosphate storage (q PP) and growth (μ PAO) of polyphosphate-accumulating organisms (PAOs) at 28 and 32 °C were found to be much higher than those reported by previous studies. Besides, the value of the stoichiometric parameter for the requirement of polyphosphate for PHA storage (Y PO4) was found to decrease as temperature rose from 28 to 32 °C. Values of two other stoichiometric parameters, i.e. the growth yield of heterotrophic organisms (Y H) and PAOs (Y PAO), were high at both temperatures. These calibrated parameters imply that the extremely active PAOs of the study were able to store PHA, store polyphosphate and even utilize PHA for cell growth. Besides, the parameters do not follow the Arrhenius correlation due to the previously reported unique microbial clade at 28 and 32 °C, which actively performs EBPR at high temperatures.

Matched MeSH terms: Glycogen/chemistry
Optimization of nitrogen and phosphorus limitation for better biodegradable plastic production and organic removal using single fed-batch mixed cultures and renewable resources

Din MF, Ujang Z, van Loosdrecht MC, Ahmad A, Sairan MF

Water Sci Technol, 2006;53(6):15-20.
PMID: 16749434

The process for the production of biodegradable plastic material (polyhydroxyalkanoates, PHAs) from microbial cells by mixed-bacterial cultivation using readily available waste (renewable resources) is the main consideration nowadays. These observations have shown impressive results typically under high carbon fraction, COD/N and COD/P (usually described as nutrient-limiting conditions) and warmest temperature (moderate condition). Therefore, the aim of this work is predominantly to select mixed cultures under high storage responded by cultivation on a substrate - non limited in a single batch reactor with shortest period for feeding and to characterize their storage response by using specific and kinetics determination. In that case, the selected-fixed temperature is 30 degrees C to establish tropical conditions. During the accumulated steady-state period, the cell growth was inhibited by high PHA content within the cells because of the carbon reserve consumption. From the experiments, there is no doubt about the PHA accumulation even at high carbon fraction ratio. Apparently, the best accumulation occurred at carbon fraction, 160 +/- 7.97 g COD/g N (PHAmean, = 44.54% of dried cells). Unfortunately, the highest PHA productivity was achieved at the high carbon fraction, 560 +/- 1.62 g COD/g N (0.152 +/- 0.17 g/l. min). Overall results showed that with high carbon fraction induced to the cultivation, the PO4 and NO3 can remove up to 20% in single cultivation.

Matched MeSH terms: Glycogen/chemistry
Glycogen-rich clear cell carcinoma in the tongue

Rajab E, Akmal SN, Nasir AM

J Laryngol Otol, 1994 Aug;108(8):716-8.
PMID: 7930932

The case of a minor salivary gland tumour, arising from the tongue, with nodal metastasis is presented. Biopsy of the tumour and fine-needle aspiration cytology of the neck swelling showed the presence of a clear cell carcinoma with evidence of nodal metastases. A commando operation was performed and the defect was reconstructed using a local tongue flap. The literature review indicated that the neoplasm was rare and its site of occurrence rather unusual.

Matched MeSH terms: Glycogen/metabolism*
Fulltext Anti-malarial Activities of Two Soil Actinomycete Isolates from Sabah via Inhibition of Glycogen Synthase Kinase 3β

Dahari DE, Salleh RM, Mahmud F, Chin LP, Embi N, Sidek HM

Trop Life Sci Res, 2016 Aug;27(2):53-71.
PMID: 27688851 MyJurnal DOI: 10.21315/tlsr2016.27.2.5

Exploiting natural resources for bioactive compounds is an attractive drug discovery strategy in search for new anti-malarial drugs with novel modes of action. Initial screening efforts in our laboratory revealed two preparations of soil-derived actinomycetes (H11809 and FH025) with potent anti-malarial activities. Both crude extracts showed glycogen synthase kinase 3β (GSK3β)-inhibitory activities in a yeast-based kinase assay. We have previously shown that the GSK3 inhibitor, lithium chloride (LiCl), was able to suppress parasitaemia development in a rodent model of malarial infection. The present study aims to evaluate whether anti-malarial activities of H11809 and FH025 involve the inhibition of GSK3β. The acetone crude extracts of H11809 and FH025 each exerted strong inhibition on the growth of Plasmodium falciparum 3D7 in vitro with 50% inhibitory concentration (IC50) values of 0.57 ± 0.09 and 1.28 ± 0.11 µg/mL, respectively. The tested extracts exhibited Selectivity Index (SI) values exceeding 10 for the 3D7 strain. Both H11809 and FH025 showed dosage-dependent chemo-suppressive activities in vivo and improved animal survivability compared to non-treated infected mice. Western analysis revealed increased phosphorylation of serine (Ser 9) GSK3β (by 6.79 to 6.83-fold) in liver samples from infected mice treated with H11809 or FH025 compared to samples from non-infected or non-treated infected mice. A compound already identified in H11809 (data not shown), dibutyl phthalate (DBP) showed active anti-plasmodial activity against 3D7 (IC50 4.87 ± 1.26 µg/mL which is equivalent to 17.50 µM) and good chemo-suppressive activity in vivo (60.80% chemo-suppression at 300 mg/kg body weight [bw] dosage). DBP administration also resulted in increased phosphorylation of Ser 9 GSK3β compared to controls. Findings from the present study demonstrate that the potent anti-malarial activities of H11809 and FH025 were mediated via inhibition of host GSK3β. In addition, our study suggests that DBP is in part the bioactive component contributing to the anti-malarial activity displayed by H11809 acting through the inhibition of GSK3β.

Matched MeSH terms: Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta
Fulltext Regulatory role of GSK3β in the activation of NF-κB and modulation of cytokine levels in Burkholderia pseudomallei-infected PBMC isolated from streptozotocin-induced diabetic animals

Maniam P, Nurul Aiezzah Z, Mohamed R, Embi N, Hasidah MS

Trop Biomed, 2015 Mar;32(1):36-48.
PMID: 25801253

Increased susceptibility of diabetics to melioidosis, a disease caused by the Burkholderia pseudomallei bacterium is believed to be attributed to dysfunction of the innate immune system. However, the underlying mechanism of the innate susceptibility is not well-understood. Glycogen synthase kinase-3β (GSK3β) plays an important role in the innate inflammatory response caused by bacterial pathogens. The present study was conducted to investigate the effects of GSK3β inhibition by LiCl on levels of pro- and anti-inflammatory cytokines; and the activity of transcription factor NF-κB in B. pseudomallei-infected peripheral blood mononuclear cells (PBMC) derived from diabetic-induced and normal Sprague Dawley rats. In addition, the effects of LiCl on intracellular bacterial counts were also investigated. Infection of PBMC from diabetic and normal rats with B. pseudomallei resulted in elevated levels of cytokines (TNF-α, IL-12 and IL-10) and phosphorylation of NF-κB in both cell types. Intracellular bacterial counts decreased with time in both cell types during infection. However bacterial clearance was less prominent in diabetic PBMC. Burkholderia pseudomallei infection also caused inactivation (Ser9 phosphorylation) of GSK3β in normal PBMC, an effect absent in infected diabetic PBMC. Inhibition of GSK3β by LiCl lowered the levels of pro-inflammatory cytokines (TNF-α and IL-12) in both normal and diabetic PBMC. Similarly, phosphorylated NF- κB (pNF-κB) levels in both cell types were decreased with LiCl treatment. Also, LiCl was able to significantly decrease the intracellular bacterial count in normal as well as diabetic PBMC. Interestingly, the levels of anti-inflammatory cytokine IL-10 in both normal and diabetic PBMC were further elevated with GSK3β inhibition. More importantly, GSK3β in infected diabetic PBMC was inactivated as in their non-diabetic counterparts upon LiCl treatment. Taken together, our results suggest that inhibition of dysregulated GSK3β in diabetic PBMC resulted in the inactivation of NF-κB and modulation of inflammatory cytokine levels. This is evidence that dysregulation of GSK3β is a contributing factor in the molecular basis of innate dysfunction and susceptibility of diabetic host to melioidosis infection.

Matched MeSH terms: Glycogen Synthase Kinase 3/antagonists & inhibitors; Glycogen Synthase Kinase 3/metabolism*
Fulltext Rhinacanthus nasutus Improves the Levels of Liver Carbohydrate, Protein, Glycogen, and Liver Markers in Streptozotocin-Induced Diabetic Rats

Visweswara Rao P, Madhavi K, Dhananjaya Naidu M, Gan SH

Evid Based Complement Alternat Med, 2013;2013:102901.
PMID: 24204387 DOI: 10.1155/2013/102901

The present study was designed to investigate the total carbohydrate, total protein, and glycogen levels in the liver and to measure functional liver markers such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in streptozotocin-(STZ-) induced diabetic rats after treatment with methanolic extract of Rhinacanthus nasutus (R. nasutus). The methanolic extract of R. nasutus was orally administered at 200 mg/kg/day while glibenclamide was administered at 50 mg/kg/day. All animals were treated for 30 days before being sacrificed. The amounts of carbohydrate, glycogen, proteins, and liver markers (AST and ALT) were measured in the liver tissue of the experimental animals. The levels of carbohydrate, glycogen, and proteins were significantly reduced in the diabetic rats but were augmented considerably after 30 days of R. nasutus treatment. The elevated AST and ALT levels in diabetic rats showed a significant decline after treatment with R. nasutus for 30 days. These results show that the administration of R. nasutus ameliorates the altered levels of carbohydrate, glycogen, proteins, and AST and ALT observed in diabetic rats and indicate that R. nasutus restores overall metabolism and liver function in experimental diabetic rats. In conclusion, the outcomes of the present study support the traditional belief that R. nasutus could ameliorate the diabetic state.

Matched MeSH terms: Glycogen
Fulltext Primary malignant melanoma of vagina: the options of management

Ng, B.K., Lim, P.S., Ng, Y.L., Kew, T.Y., Abdul Kadir, A.K., Hatta, M.

Journal of Surgical Academia, 2014;4(1):63-66.
MyJurnal

Primary malignant melanoma of the vagina is rare but aggressive. Various treatment options include surgery and adjuvant therapy has been advocated but the outcome remained unpredictable. Standard treatment protocol is yet to be established. We report a case of 54-year-old, Para 4+1, with malignant melanoma of the vagina. She underwent wide local excision but the surgical margin was not clear of malignant cells, hence adjuvant radiotherapy was given. Combination chemotherapy was initiated subsequently as her disease disseminated. She succumbed later due to septicaemic shock. The treatment options for vaginal melanoma were reviewed.

Matched MeSH terms: Glycogen Storage Disease Type VI
Fulltext TG-SK, a teak (Tectona grandis Linn.) homolog of GSK-3/ shaggy protein kinase

Norlia B., Norwati M., Norwati A., Mohd Rosli H., Norihan M. S.

Buletin Persatuan Genetik Malaysia, 2006;12(1):7-8.
MyJurnal

This study was part of the larger studies to isolate and characterize gene related to flowering in teak. This study isolated differentially expressed genes of teak flowering tissues. One of the genes encodes plant protein kinases highly homologous to the AtSK-II of Arabidopsis GSK3/SHAGGY subfamily. The gene was named as Tectona grandis SHAGGY kinase (Tg-SK). The protein sequence of this gene contained the characteristic catalytic domain of GSK-3/SHAGGY protein kinase. The gene also shows the same genomic organization of 11 introns and 12 exons. Although the size of the introns varies, the positions of exon/intron boundaries are very similar to AtSK-II. The discovery of this gene in teak, which is a forest tree species, supports the hypothesis, which suggested the gene is found in all eukaryotes.

Matched MeSH terms: Glycogen Synthase Kinase 3
Fulltext Tamarindus indica seeds improve carbohydrate and lipid metabolism: An in vivo study

Uchenna UE, Shori AB, Baba AS

J Ayurveda Integr Med, 2017 12 06;9(4):258-265.
PMID: 29203351 DOI: 10.1016/j.jaim.2017.06.004

BACKGROUND: The tamarind seeds have a lot of nutrients that may be used to control cholesterol or glucose levels.
OBJECTIVE(S): The effects of tamarind seeds (T) on lipid and carbohydrate metabolism in rats were studied. Rats were offered basal diet (BD) with T (2%, 4% or 8%) or without T.
MATERIALS AND METHODS: Feeding and growth performance in rats were measured and samples of liver and blood were analyzed for glycogen content and levels of cholesterol and glucose respectively.
RESULTS: The inclusion of T in the diet influences the feeding and growth performance in rats. The serum cholesterol level was reduced (p glycogen storage in livers of SD rats fed on BD and high sucrose diet.
CONCLUSION: Tamarind seeds can lower blood glucose and serum cholesterol and enhance storage of glycogen in rats.

Matched MeSH terms: Glycogen
The Antimalarial Effect of Curcumin Is Mediated by the Inhibition of Glycogen Synthase Kinase-3β

Ali AH, Sudi S, Basir R, Embi N, Sidek HM

J Med Food, 2017 Feb;20(2):152-161.
PMID: 28146408 DOI: 10.1089/jmf.2016.3813

Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (GSK3β)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3β. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development. At the highest dose tested (30 mg/kg body weight), both therapeutic and prophylactic administrations of curcumin resulted in suppression exceeding 50% and improved median survival time of infected mice compared to control. Western analysis revealed a 5.5-fold (therapeutic group) and 1.8-fold (prophylactic group) increase in phosphorylation of Ser 9 GSK3β and 1.6-fold (therapeutic group) and 1.7-fold (prophylactic group) increase in Ser 473 Akt in liver of curcumin-treated infected animals. Following P. berghei infection, levels of pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, and IL-4 were elevated by 7.5-, 35.0-, 33.0-, and 2.2-fold, respectively. Curcumin treatment (therapeutic) caused a significant decrease (by 6.0- and 2.0-fold, respectively) in serum TNF-α and IFN-γ level, while IL-10 and IL-4 were elevated (by 1.4- and 1.8-fold). Findings from the present study demonstrate for the first time that the antimalarial action of curcumin involved inhibition of GSK3β.

Matched MeSH terms: Glycogen Synthase Kinase 3 beta/antagonists & inhibitors*; Glycogen Synthase Kinase 3 beta/genetics; Glycogen Synthase Kinase 3 beta/metabolism
Fulltext Manilkara zapota (L.) P. Royen leaf water extract triggered apoptosis and activated caspase-dependent pathway in HT-29 human colorectal cancer cell line

Tan BL, Norhaizan ME

Biomed Pharmacother, 2019 Feb;110:748-757.
PMID: 30554113 DOI: 10.1016/j.biopha.2018.12.027

Manilkara zapota (L.) P. Royen (Family: Sapotaceae), commonly called as sapodilla, has been applied as traditional folk medicine for diarrhea and pulmonary infections. Conventional therapy in colorectal cancer is not likely effective due to undesirable outcomes. The anti-colon cancer properties of Manilkara zapota leaf water extract have yet to be investigated thus far. Therefore, our present study aimed to evaluate the ability to induce apoptosis and the underlying mechanisms of Manilkara zapota leaf water extract against human colorectal cancer (HT-29) cells. The cytotoxicity of Manilkara zapota leaf water extract was screened in different cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyses. The morphological changes in HT-29 cell lines after exposure to Manilkara zapota leaf water extract were viewed under fluorescence and inverted light microscope. The apoptotic cell was measured by Annexin V-propidium iodide staining. The caspase-3 and -8 activities were assessed by colorimetric assay. Overall analyses revealed that treatment with Manilkara zapota leaf water extract for 72 h can inhibit the viability of HT-29 cells. Incubation with Manilkara zapota leaf water extract for 24, 48, and 72 h significantly increased (p < 0.05) the total apoptotic cells compared to the control. Treatment with 21, 42, and 84 μg/mL of Manilkara zapota leaf water extract for 72 h triggered both caspase-3 and -8 activities in a concentration-dependent pattern. We also found that the catalase level in the two treatment groups (21 and 42 μg/mL) was significantly elevated after 24 h incubation. Incubation with Manilkara zapota leaf water extract for 72 h triggered the transcriptional elevation of the adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK3β), AXIN1, and casein kinase 1 (CK1). The β-catenin mRNA levels were reduced accordingly when the concentration of the Manilkara zapota leaf water extract was increased. Our results suggested that Manilkara zapota leaf water extract offer great potential against colorectal cancer through modulation of Wnt/β-catenin signaling pathway, caspase-dependent pathway, and antioxidant enzyme.

Matched MeSH terms: Glycogen Synthase Kinase 3 beta

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