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Fulltext Potential effects of chrysin on MDA-MB-231 cells

Hong TB, Rahumatullah A, Yogarajah T, Ahmad M, Yin KB

Int J Mol Sci, 2010;11(3):1057-69.
PMID: 20479999 DOI: 10.3390/ijms11031057

This study aims to elucidate the effects of chrysin on human ER-negative breast cancer cell line, MDA-MB-231. The study demonstrated that treatment of MDA-MB-231 cells with 20 microM chysin for 48 h significantly inhibited the growth of MDA-MB-231 cells and induced cytoplasmic lipid accumulation in the cells, but that the observed of cell death was not caused by apoptosis. The expression of PPARalpha mRNA in chrysin-treated MDA-MB-231 cells was significantly increased, which was likely associated to the proliferation of the cells post chrysin treatment.

Matched MeSH terms: Cell Line, Tumor
Fulltext CRNDE: A Pivotal Oncogenic Long Non-Coding RNA in Cancers

Hor YZ, Salvamani S, Gunasekaran B, Yian KR

Yale J Biol Med, 2023 Dec;96(4):511-526.
PMID: 38161583 DOI: 10.59249/VHYE2306

Colorectal Neoplasia Differentially Expressed (CRNDE), a long non-coding RNA that was initially identified as aberrantly expressed in colorectal cancer (CRC) has also been observed to exhibit elevated expression in various other human malignancies. Recent research has accumulated substantial evidence implicating CRNDE as an oncogenic player, exerting influence over critical cellular processes linked to cancer progression. Particularly, its regulatory interactions with microRNAs and proteins have been shown to modulate pathways that contribute to carcinogenesis and tumorigenesis. This review will comprehensively outline the roles of CRNDE in colorectal, liver, glioma, lung, cervical, gastric and prostate cancer, elucidating the mechanisms involved in modulating proliferation, apoptosis, migration, invasion, angiogenesis, and radio/chemoresistance. Furthermore, the review highlights CRNDE's potential as a multifaceted biomarker, owing to its presence in diverse biological samples and stable properties, thereby underscoring its diagnostic, therapeutic, and prognostic applications. This review aims to provide comprehensive insights of CRNDE-mediated oncogenesis and identify CRNDE as a promising target for future clinical interventions.

Matched MeSH terms: Cell Line, Tumor
Synthesis, Molecular Docking, and Biological Evaluation of Benzimidazole Derivatives as Selective Butyrylcholinesterase Inhibitors

Ha ZY, Ong HC, Oo CW, Yeong KY

Curr Alzheimer Res, 2020;17(13):1177-1185.
PMID: 33602088 DOI: 10.2174/1567205018666210218151228

BACKGROUND: Benzimidazole is an interesting pharmacophore which has been extensively studied in medicinal chemistry due to its high affinity towards various enzymes and receptors. Its derivatives have been previously shown to possess a wide range of biological activities including anthelmintic, antihypertensive, antiulcer, as well as anticholinesterase activity.
OBJECTIVE: The objective of this study is to search for more potent benzimidazole-based cholinesterase inhibitors, through the modification of the 1- and 2-positions of the benzimidazole core.
METHODS: Synthesis of compounds were carried out via a 4-step reaction scheme following a previously reported protocol. Structure-activity relationship of the compounds are established through in vitro cholinesterase assays and in silico docking studies. Furthermore, cytotoxicity and blood brain barrier (BBB) permeability of the compounds were also investigated.
RESULTS: Among the synthesised compounds, three of them (5IIa, 5IIb, and 5IIc) exhibited potent selective butyrylcholinesterase inhibition at low micromolar level. The compounds did not show any significant cytotoxicity when tested against a panel of human cell lines. Moreover, the most active compound, 5IIc, was highly permeable across the blood brain barrier.
CONCLUSION: In total 10 benzimidazole derivatives were synthesized and screened for their AChE and BuChE inhibitory activities. Lead compound 5Iic, represents a valuable compound for further development as potential AD therapeutics.

Matched MeSH terms: Cell Line
Fulltext Hyperhomocysteinemia causes ER stress and impaired autophagy that is reversed by Vitamin B supplementation

Tripathi M, Zhang CW, Singh BK, Sinha RA, Moe KT, DeSilva DA, et al.

Cell Death Dis, 2016 12 08;7(12):e2513.
PMID: 27929536 DOI: 10.1038/cddis.2016.374

Hyperhomocysteinemia (HHcy) is a well-known risk factor for stroke; however, its underlying molecular mechanism remains unclear. Using both mouse and cell culture models, we have provided evidence that impairment of autophagy has a central role in HHcy-induced cellular injury in the mouse brain. We observed accumulation of LC3B-II and p62 that was associated with increased MTOR signaling in human and mouse primary astrocyte cell cultures as well as a diet-induced mouse model of HHcy, HHcy decreased lysosomal membrane protein LAMP2, vacuolar ATPase (ATP6V0A2), and protease cathepsin D, suggesting that lysosomal dysfunction also contributed to the autophagic defect. Moreover, HHcy increased unfolded protein response. Interestingly, Vitamin B supplementation restored autophagic flux, alleviated ER stress, and reversed lysosomal dysfunction due to HHCy. Furthermore, the autophagy inducer, rapamycin was able to relieve ER stress and reverse lysosomal dysfunction caused by HHcy in vitro. Inhibition of autophagy by HHcy exacerbated cellular injury during oxygen and glucose deprivation and reperfusion (OGD/R), and oxidative stress. These effects were prevented by Vitamin B co-treatment, suggesting that it may be helpful in relieving detrimental effects of HHcy in ischemia/reperfusion or oxidative stress. Collectively, these findings show that Vitamin B therapy can reverse defects in cellular autophagy and ER stress due to HHcy; and thus may be a potential treatment to reduce ischemic damage caused by stroke in patients with HHcy.

Matched MeSH terms: Cell Line, Tumor
Fulltext Effects of the Sintering Process on Nacre-Derived Hydroxyapatite Scaffolds for Bone Engineering

Megat Abdul Wahab R, Abdullah N, Zainal Ariffin SH, Che Abdullah CA, Yazid F

Molecules, 2020 Jul 08;25(14).
PMID: 32650572 DOI: 10.3390/molecules25143129

A hydroxyapatite scaffold is a suitable biomaterial for bone tissue engineering due to its chemical component which mimics native bone. Electronic states which present on the surface of hydroxyapatite have the potential to be used to promote the adsorption or transduction of biomolecules such as protein or DNA. This study aimed to compare the morphology and bioactivity of sinter and nonsinter marine-based hydroxyapatite scaffolds. Field emission scanning electron microscopy (FESEM) and micro-computed tomography (microCT) were used to characterize the morphology of both scaffolds. Scaffolds were co-cultured with 5 × 104/cm2 of MC3T3-E1 preosteoblast cells for 7, 14, and 21 days. FESEM was used to observe the cell morphology, and MTT and alkaline phosphatase (ALP) assays were conducted to determine the cell viability and differentiation capacity of cells on both scaffolds. Real-time polymerase chain reaction (rtPCR) was used to identify the expression of osteoblast markers. The sinter scaffold had a porous microstructure with the presence of interconnected pores as compared with the nonsinter scaffold. This sinter scaffold also significantly supported viability and differentiation of the MC3T3-E1 preosteoblast cells (p < 0.05). The marked expression of Col1α1 and osteocalcin (OCN) osteoblast markers were also observed after 14 days of incubation (p < 0.05). The sinter scaffold supported attachment, viability, and differentiation of preosteoblast cells. Hence, sinter hydroxyapatite scaffold from nacreous layer is a promising biomaterial for bone tissue engineering.

Matched MeSH terms: Cell Line
Isolation, identification and characterization of chicken anaemia virus in Malaysia

Chowdhury SM, Omar AR, Aini I, Hair-Bejo M, Jamaluddin AA, Kono Y, et al.

J. Biochem. Mol. Biol. Biophys., 2002 Aug;6(4):249-55.
PMID: 12186740

A study was conducted to isolate and identify chicken anaemia virus (CAV) from field samples of clinically infected broiler chickens in Malaysia. A total of 125 samples were collected from chickens aged 2-6 weeks with clinically depressed and retarded growth, of which five samples were found positive to CAV directly by polymerase chain reaction (PCR). Later, five isolates of CAV from the respective five PCR positive samples were isolated in MDCC-MSB1 cells at passage 4 based on cytopathic effects, PCR and indirect immunofluorescent antibody test. The isolates were identified as BL-1, BL-2, BL-3, BL-4 and BL-5. These CAV isolates were found to resist treatment with chloroform and heat at 37 degrees C for 2 h, 56 degrees C for 30 min and 70 degrees C for 5 min. One of the isolates, BL-5 produced significant reduction (p < 0.001) of hematocrit values (9-19%), pale bone marrow, thymus atrophy and haemorrhages in skin/muscle when inoculated into 1-day old SPF chickens. Restriction enzyme digestion of 926 bp genomic fragments of all the isolates including Cux-1 isolate with HindIII exhibited a similar pattern of bands in 2% agarose gel. The present findings confirmed the presence of CAV in Malaysia.

Matched MeSH terms: Cell Line
A newly isolated probiotic Enterococcus faecalis strain from vagina microbiota enhances apoptosis of human cancer cells

Nami Y, Abdullah N, Haghshenas B, Radiah D, Rosli R, Yari Khosroushahi A

J Appl Microbiol, 2014 Aug;117(2):498-508.
PMID: 24775273 DOI: 10.1111/jam.12531

This study aimed to describe probiotic properties and bio-therapeutic effects of newly isolated Enterococcus faecalis from the human vaginal tract.

Matched MeSH terms: Cell Line; Cell Line, Tumor
Replication of a malaysian strain avian influenza a virus H5N1 in madin-darby canine kidney and african green monkey kidney cells

Tan TS, Sharifah Syed Hassan, Yap WB

Sains Malaysiana, 2016;45:787-793.

The use of cell lines such as Madin-Darby Canine Kidney (MDCK) and African Green Monkey Kidney (Vero) cells in
influenza vaccine production is much advocated presently as a safer alternative to chicken embryonated eggs. It is
thus essential to understand the influenza virus replication patterns in these cell lines prior to utilizing them in vaccine
production. The infectivity of avian influenza A virus (A/Chicken/Malaysia/5858/2004) H5N1 in MDCK and Vero cell
lines was first assessed by comparing the cytopathic effect (CPE) caused by the virus infection. The viral loads in both
of the infected media and cells were also compared. The results showed that both of the MDCK and Vero cells began to
exhibit significant CPE (p<0.05) after 48 h post-infection (h p.i). The MDCK cell line was more susceptible to the virus
infection compared to Vero cell line throughout the incubation period. A higher viral load was also detected in the host
cells compared to their respective culturing media. Interestingly, after reaching its maximum titer at 48 h p.i, the viral
load in MDCK cells declined meanwhile the viral load in Vero cells increased gradually and peaked at 120 h p.i. Overall,
both cell lines support efficient H5N1 virus replication. While the peak viral loads measured in the two cell lines did
not differ much, a more rapid replication was observed in the infected MDCK samples. The finding showed that MDCK
cell line might serve as a more time-saving and cost-effective cell culture-based system compared to Vero cell line for
influenza vaccine production.

Matched MeSH terms: Cell Line
Fulltext Monoamine oxidase A is down-regulated in EBV-associated nasopharyngeal carcinoma

Lee HM, Sia APE, Li L, Sathasivam HP, Chan MSA, Rajadurai P, et al.

Sci Rep, 2020 04 09;10(1):6115.
PMID: 32273550 DOI: 10.1038/s41598-020-63150-0

Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we identify for the first time a role for monoamine oxidase A (MAOA) in NPC. MAOA is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines. Depending on the cancer type, MAOA can either have a tumour-promoting or tumour-suppressive role. We show that MAOA is down-regulated in primary NPC tissues and its down-regulation enhances the migration of NPC cells. In addition, we found that EBV infection can down-regulate MAOA expression in both pre-malignant and malignant nasopharyngeal epithelial (NPE) cells. We further demonstrate that MAOA is down-regulated as a result of IL-6/IL-6R/STAT3 signalling and epigenetic mechanisms, effects that might be attributed to EBV infection in NPE cells. Taken together, our data point to a central role for EBV in mediating the tumour suppressive effects of MAOA and that loss of MAOA could be an important step in the pathogenesis of NPC.

Matched MeSH terms: Cell Line, Tumor
Fulltext Oncogenic S1P signalling in EBV-associated nasopharyngeal carcinoma activates AKT and promotes cell migration through S1P receptor 3

Lee HM, Lo KW, Wei W, Tsao SW, Chung GTY, Ibrahim MH, et al.

J Pathol, 2017 05;242(1):62-72.
PMID: 28240350 DOI: 10.1002/path.4879

Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1, and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration. We also show that S1P receptor 3 (S1PR3) mRNA is overexpressed in EBV-positive NPC patient-derived xenografts and a subset of primary NPC tissues, and that knockdown of S1PR3 suppressed the activation of AKT and the S1P-induced migration of NPC cells. Taken together, our data point to a central role for EBV in mediating the oncogenic effects of S1P in NPC and identify S1P signalling as a potential therapeutic target in this disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Matched MeSH terms: Cell Line, Tumor
Fractionation and Biological Activities of Water-Soluble Polysaccharides from Sclerotium of Tiger Milk Medicinal Mushroom, Lignosus rhinocerotis (Agaricomycetes)

Keong CY, B V, Daker M, Hamzah MY, Mohamad SA, Lan J, et al.

Int J Med Mushrooms, 2016;18(2):141-54.
PMID: 27279536 DOI: 10.1615/IntJMedMushrooms.v18.i2.50

This study investigated antioxidant and anti-inflammatory properties, and the direct cytotoxic effect of Lignosus rhinocerotis fractions, especially the polysaccharide fraction, on nasopharyngeal carcinoma cells. L. rhinocerotis crude extract was obtained through hot water extraction. The precipitate saturated with 30% ammonium sulfate was purified with ion-exchanged chromatography. Gel permeation chromatography multiangle laser light scattering analysis equipped with light scattering and UV signals revealed two district groups of polymers. A total of four peaks were observed in the total carbohydrate test. Fraction C, which was the second region of the second peak eluted with 0.3 M NaOH, showed the highest integrated molecular weight, whereas fraction E had the lowest integrated molecular weight of 19,790 Da. Fraction A contained the highest β-D-glucan content. Enzymatic analysis showed that most of the polysaccharide fractions contained β-1-3 and β-1-6 skeletal backbones. The peak eluted with 0.6 M NaOH was separated in fraction D (flask 89-92) and fraction E (93-96). The results showed that fraction E expressed higher antioxidant activities than fraction D whereas fraction D expressed higher chelating activity than fraction E. The extract saturated with 30% ammonium sulfate exhibited higher reducing power than the extract saturated with 100% ammonium sulfate. Fractions D and E significantly inhibited the secretion of tumor necrosis factor-α in lipopolysaccharide-stimulated RAW 264.7 macrophages in a dose-dependent manner. There was no apparent difference in the viability of cells exposed or unexposed to L. rhinocerotis fractions.

Matched MeSH terms: Cell Line, Tumor
Fulltext Expression of Endogenous Angiotensin-Converting Enzyme 2 in Human Induced Pluripotent Stem Cell-Derived Retinal Organoids

Ahmad Mulyadi Lai HI, Chou SJ, Chien Y, Tsai PH, Chien CS, Hsu CC, et al.

Int J Mol Sci, 2021 Jan 28;22(3).
PMID: 33525682 DOI: 10.3390/ijms22031320

Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal organoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.

Matched MeSH terms: Cell Line
Degradation of MicroRNA miR-466d-3p by Japanese Encephalitis Virus NS3 Facilitates Viral Replication and Interleukin-1β Expression

Jiang H, Bai L, Ji L, Bai Z, Su J, Qin T, et al.

J Virol, 2020 07 16;94(15).
PMID: 32461319 DOI: 10.1128/JVI.00294-20

Japanese encephalitis virus (JEV) infection alters microRNA (miRNA) expression in the central nervous system (CNS). However, the mechanism contributing to miRNA regulation in the CNS is not known. We discovered global degradation of mature miRNA in mouse brains and neuroblastoma (NA) cells after JEV infection. Integrative analysis of miRNAs and mRNAs suggested that several significantly downregulated miRNAs and their targeted mRNAs were clustered into an inflammation pathway. Transfection with miRNA 466d-3p (miR-466d-3p) decreased interleukin-1β (IL-1β) expression and inhibited JEV replication in NA cells. However, miR-466d-3p expression increased after JEV infection in the presence of cycloheximide, indicating that viral protein expression reduced miR-466d-3p expression. We generated all the JEV coding proteins and demonstrated NS3 helicase protein to be a potent miRNA suppressor. The NS3 proteins of Zika virus, West Nile virus, and dengue virus serotype 1 (DENV-1) and DENV-2 also decreased miR-466d-3p expression. Results from helicase-blocking assays and in vitro unwinding assays demonstrated that NS3 could unwind pre-miR-466d and induce miRNA dysfunction. Computational models and an RNA immunoprecipitation assay revealed arginine-rich domains of NS3 to be crucial for pre-miRNA binding and degradation of host miRNAs. Importantly, site-directed mutagenesis of conserved residues in NS3 revealed that R226G and R202W reduced the binding affinity and degradation of pre-miR-466d. These results expand the function of flavivirus helicases beyond unwinding duplex RNA to degrade pre-miRNAs. Hence, we revealed a new mechanism for NS3 in regulating miRNA pathways and promoting neuroinflammation.IMPORTANCE Host miRNAs have been reported to regulate JEV-induced inflammation in the CNS. We found that JEV infection could reduce expression of host miRNA. The helicase region of the NS3 protein bound specifically to miRNA precursors and could lead to incorrect unwinding of miRNA precursors, thereby reducing the expression of mature miRNAs. This observation led to two major findings. First, our results suggested that JEV NS3 protein induced miR-466d-3p degradation, which promoted IL-1β expression and JEV replication. Second, arginine molecules on NS3 were the main miRNA-binding sites, because we demonstrated that miRNA degradation was abolished if arginines at R226 and R202 were mutated. Our study provides new insights into the molecular mechanism of JEV and reveals several amino acid sites that could be mutated for a JEV vaccine.

Matched MeSH terms: Cell Line, Tumor
Fulltext Key drug-targeting genes in pancreatic ductal adenocarcinoma

Sakharkar MK, Dhillon SK, Mazumder M, Yang J

Genes Cancer, 2021;12:12-24.
PMID: 33884102 DOI: 10.18632/genesandcancer.210

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal type of cancer. In this study, we undertook a pairwise comparison of gene expression pattern between tumor tissue and its matching adjacent normal tissue for 45 PDAC patients and identified 22 upregulated and 32 downregulated genes. PPI network revealed that fibronectin 1 and serpin peptidase inhibitor B5 were the most interconnected upregulated-nodes. Virtual screening identified bleomycin exhibited reasonably strong binding to both proteins. Effect of bleomycin on cell viability was examined against two PDAC cell lines, AsPC-1 and MIA PaCa-2. AsPC-1 did not respond to bleomycin, however, MIA PaCa-2 responded to bleomycin with an IC50 of 2.6 μM. This implicates that bleomycin could be repurposed for the treatment of PDAC, especially in combination with other chemotherapy agents. In vivo mouse xenograft studies and patient clinical trials are warranted to understand the functional mechanism of bleomycin towards PDAC and optimize its therapeutic efficacy. Furthermore, we will evaluate the antitumor activity of the other identified drugs in our future studies.

Matched MeSH terms: Cell Line
Fulltext Human papillomavirus type 16 E7 oncoprotein mediates CCNA1 promoter methylation

Chalertpet K, Pakdeechaidan W, Patel V, Mutirangura A, Yanatatsaneejit P

Cancer Sci, 2015 Oct;106(10):1333-40.
PMID: 26250467 DOI: 10.1111/cas.12761

Human papillomavirus (HPV) oncoproteins drive distinctive promoter methylation patterns in cancer. However, the underlying mechanism remains to be elucidated. Cyclin A1 (CCNA1) promoter methylation is strongly associated with HPV-associated cancer. CCNA1 methylation is found in HPV-associated cervical cancers, as well as in head and neck squamous cell cancer. Numerous pieces of evidence suggest that E7 may drive CCNA1 methylation. First, the CCNA1 promoter is methylated in HPV-positive epithelial lesions after transformation. Second, the CCNA1 promoter is methylated at a high level when HPV is integrated into the human genome. Finally, E7 has been shown to interact with DNA methyltransferase 1 (Dnmt1). Here, we sought to determine the mechanism by which E7 increases methylation in cervical cancer by using CCNA1 as a gene model. We investigated whether E7 induces CCNA1 promoter methylation, resulting in the loss of expression. Using both E7 knockdown and overexpression approaches in SiHa and C33a cells, our data showed that CCNA1 promoter methylation decreases with a corresponding increase in expression in E7 siRNA-transfected cells. By contrast, CCNA1 promoter methylation was augmented with a corresponding reduction in expression in E7-overexpressing cells. To confirm whether the binding of the E7-Dnmt1 complex to the CCNA1 promoter induced methylation and loss of expression, ChIP assays were carried out in E7-, del CR3-E7 and vector control-overexpressing C33a cells. The data showed that E7 induced CCNA1 methylation by forming a complex with Dnmt1 at the CCNA1 promoter, resulting in the subsequent reduction of expression in cancers. It is interesting to further explore the genome-wide mechanism of E7 oncoprotein-mediated DNA methylation.

Matched MeSH terms: Cell Line, Tumor
Fulltext Adipocytokine Regulation and Antiangiogenic Activity Underlie the Molecular Mechanisms of Therapeutic Effects of Phyllanthus niruri against Non-Alcoholic Fatty Liver Disease

Zarzour RHA, Alshawsh MA, Asif M, Al-Mansoub MA, Mohamed Z, Ahmad M, et al.

Nutrients, 2018 Aug 09;10(8).
PMID: 30096951 DOI: 10.3390/nu10081057

The growth of adipose tissues is considered angiogenesis-dependent during non-alcoholic fatty liver disease (NAFLD). We have recently reported that our standardized 50% methanolic extract (ME) of Phyllanthus niruri (50% ME of P. niruri) has alleviated NAFLD in Sprague⁻Dawley rats. This study aimed to assess the molecular mechanisms of action, and to further evaluate the antiangiogenic effect of this extract. NAFLD was induced by eight weeks of high-fat diet, and treatment was applied for four weeks. Antiangiogenic activity was assessed by aortic ring assay and by in vitro tests. Our findings demonstrated that the therapeutic effects of 50% ME among NAFLD rats, were associated with a significant increase in serum adiponectin, reduction in the serum levels of RBP4, vaspin, progranulin, TNF-α, IL-6, and significant downregulation of the hepatic gene expression of PPARγ, SLC10A2, and Collα1. Concomitantly, 50% ME of P. niruri has exhibited a potent antiangiogenic activity on ring assay, cell migration, vascular endothelial growth factor (VEGF), and tube formation, without any cytotoxic effect. Together, our findings revealed that the protective effects of P. niruri against NAFLD might be attributed to its antiangiogenic effect, as well as to the regulation of adipocytokines and reducing the expression of adipogenic genes.

Matched MeSH terms: Cell Line
Fulltext Human cytomegalovirus may promote tumour progression by upregulating arginase-2

Costa H, Xu X, Overbeek G, Vasaikar S, Patro CP, Kostopoulou ON, et al.

Oncotarget, 2016 Jul 26;7(30):47221-47231.
PMID: 27363017 DOI: 10.18632/oncotarget.9722

BACKGROUND: Both arginase (ARG2) and human cytomegalovirus (HCMV) have been implicated in tumorigenesis. However, the role of ARG2 in the pathogenesis of glioblastoma (GBM) and the HCMV effects on ARG2 are unknown. We hypothesize that HCMV may contribute to tumorigenesis by increasing ARG2 expression.
RESULTS: ARG2 promotes tumorigenesis by increasing cellular proliferation, migration, invasion and vasculogenic mimicry in GBM cells, at least in part due to overexpression of MMP2/9. The nor-NOHA significantly reduced migration and tube formation of ARG2-overexpressing cells. HCMV immediate-early proteins (IE1/2) or its downstream pathways upregulated the expression of ARG2 in U-251 MG cells. Immunostaining of GBM tissue sections confirmed the overexpression of ARG2, consistent with data from subsets of Gene Expression Omnibus. Moreover, higher levels of ARG2 expression tended to be associated with poorer survival in GBM patient by analyzing data from TCGA.
METHODS: The role of ARG2 in tumorigenesis was examined by proliferation-, migration-, invasion-, wound healing- and tube formation assays using an ARG2-overexpressing cell line and ARG inhibitor, N (omega)-hydroxy-nor-L-arginine (nor-NOHA) and siRNA against ARG2 coupled with functional assays measuring MMP2/9 activity, VEGF levels and nitric oxide synthase activity. Association between HCMV and ARG2 were examined in vitro with 3 different GBM cell lines, and ex vivo with immunostaining on GBM tissue sections. The viral mechanism mediating ARG2 induction was examined by siRNA approach. Correlation between ARG2 expression and patient survival was extrapolated from bioinformatics analysis on data from The Cancer Genome Atlas (TCGA).
CONCLUSIONS: ARG2 promotes tumorigenesis, and HCMV may contribute to GBM pathogenesis by upregulating ARG2.

Matched MeSH terms: Cell Line, Tumor
Fulltext A comparative study of non-viral gene delivery techniques to human adipose-derived mesenchymal stem cell

Abdul Halim NS, Fakiruddin KS, Ali SA, Yahaya BH

Int J Mol Sci, 2014;15(9):15044-60.
PMID: 25162825 DOI: 10.3390/ijms150915044

Mesenchymal stem cells (MSCs) hold tremendous potential for therapeutic use in stem cell-based gene therapy. Ex vivo genetic modification of MSCs with beneficial genes of interest is a prerequisite for successful use of stem cell-based therapeutic applications. However, genetic manipulation of MSCs is challenging because they are resistant to commonly used methods to introduce exogenous DNA or RNA. Herein we compared the effectiveness of several techniques (classic calcium phosphate precipitation, cationic polymer, and standard electroporation) with that of microporation technology to introduce the plasmid encoding for angiopoietin-1 (ANGPT-1) and enhanced green fluorescent protein (eGFP) into human adipose-derived MSCs (hAD-MSCs). The microporation technique had a higher transfection efficiency, with up to 50% of the viable hAD-MSCs being transfected, compared to the other transfection techniques, for which less than 1% of cells were positive for eGFP expression following transfection. The capability of cells to proliferate and differentiate into three major lineages (chondrocytes, adipocytes, and osteocytes) was found to be independent of the technique used for transfection. These results show that the microporation technique is superior to the others in terms of its ability to transfect hAD-MSCs without affecting their proliferation and differentiation capabilities. Therefore, this study provides a foundation for the selection of techniques when using ex vivo gene manipulation for cell-based gene therapy with MSCs as the vehicle for gene delivery.

Matched MeSH terms: Cell Line
Fulltext Synergistic Roles of Curcumin in Sensitising the Cisplatin Effect on a Cancer Stem Cell-Like Population Derived from Non-Small Cell Lung Cancer Cell Lines

Abdul Satar N, Ismail MN, Yahaya BH

Molecules, 2021 Feb 18;26(4).
PMID: 33670440 DOI: 10.3390/molecules26041056

Cancer stem cells (CSCs) represent a small subpopulation within a tumour. These cells possess stem cell-like properties but also initiate resistance to cytotoxic agents, which contributes to cancer relapse. Natural compounds such as curcumin that contain high amounts of polyphenols can have a chemosensitivity effect that sensitises CSCs to cytotoxic agents such as cisplatin. This study was designed to investigate the efficacy of curcumin as a chemo-sensitiser in CSCs subpopulation of non-small cell lung cancer (NSCLC) using the lung cancer adenocarcinoma human alveolar basal epithelial cells A549 and H2170. The ability of curcumin to sensitise lung CSCs to cisplatin was determined by evaluating stemness characteristics, including proliferation activity, colony formation, and spheroid formation of cells treated with curcumin alone, cisplatin alone, or the combination of both at 24, 48, and 72 h. The mRNA level of genes involved in stemness was analysed using quantitative real-time polymerase chain reaction. Liquid chromatography-mass spectrometry was used to evaluate the effect of curcumin on the CSC niche. A combined treatment of A549 subpopulations with curcumin reduced cellular proliferation activity at all time points. Curcumin significantly (p < 0.001) suppressed colonies formation by 50% and shrank the spheroids in CSC subpopulations, indicating inhibition of their self-renewal capability. This effect also was manifested by the down-regulation of SOX2, NANOG, and KLF4. Curcumin also regulated the niche of CSCs by inhibiting chemoresistance proteins, aldehyde dehydrogenase, metastasis, angiogenesis, and proliferation of cancer-related proteins. These results show the potential of using curcumin as a therapeutic approach for targeting CSC subpopulations in non-small cell lung cancer.

Matched MeSH terms: Cell Line, Tumor
Fulltext Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines

Baharuddin P, Satar N, Fakiruddin KS, Zakaria N, Lim MN, Yusoff NM, et al.

Oncol Rep, 2016 Jan;35(1):13-25.
PMID: 26531053 DOI: 10.3892/or.2015.4371

Natural compounds such as curcumin have the ability to enhance the therapeutic effectiveness of common chemotherapy agents through cancer stem-like cell (CSC) sensitisation. In the present study, we showed that curcumin enhanced the sensitivity of the double-positive (CD166+/EpCAM+) CSC subpopulation in non-small cell lung cancer (NSCLC) cell lines (A549 and H2170) to cisplatin-induced apoptosis and inhibition of metastasis. Our results revealed that initial exposure of NSCLC cell lines to curcumin (10-40 µM) markedly reduced the percentage of viability to an average of ~51 and ~54% compared to treatment with low dose cisplatin (3 µM) with only 94 and 86% in both the A549 and H2170 cells. Moreover, sensitisation of NSCLC cell lines to curcumin through combined treatment enhanced the single effect induced by low dose cisplatin on the apoptosis of the double-positive CSC subpopulation by 18 and 20% in the A549 and H2170 cells, respectively. Furthermore, we found that curcumin enhanced the inhibitory effects of cisplatin on the highly migratory CD166+/EpCAM+ subpopulation, marked by a reduction in cell migration to 9 and 21% in the A549 and H2170 cells, respectively, indicating that curcumin may increase the sensitivity of CSCs to cisplatin-induced migratory inhibition. We also observed that the mRNA expression of cyclin D1 was downregulated, while a substantial increased in p21 expression was noted, followed by Apaf1 and caspase-9 activation in the double-positive (CD166+/EpCAM+) CSC subpopulation of A549 cells, suggested that the combined treatments induced cell cycle arrest, therefore triggering CSC growth inhibition via the intrinsic apoptotic pathway. In conclusion, we provided novel evidence of the previously unknown therapeutic effects of curcumin, either alone or in combination with cisplatin on the inhibition of the CD166+/EpCAM+ subpopulation of NSCLC cell lines. This finding demonstrated the potential therapeutic approach of using curcumin that may enhance the effects of cisplatin by targeting the CSC subpopulation in NSCLC.

Matched MeSH terms: Cell Line, Tumor

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