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Fulltext Cold allodynia as the presenting symptom in a case of acquired neuromyotonia (Isaacs syndrome) with multiple autoantibodies

Goh KJ, Abdullah S, Wong WF, Yeap SS, Shahrizaila N, Tan CT

Neurology Asia, 2014;19(4):409-412.
MyJurnal

We report a patient who presented with severe cold-induced allodynia and hyperhidrosis, and found to have acquired neuromyotonia (Isaacs syndrome) with high voltage-gated potassium channel (VGKC) antibody titre,positive contactin-associated protein 2 (CASPR2) and leucine-rich glioma-inactivated 1 (LGI1) antibodies. The patient also had positive anti-dsDNA and acetylcholine receptor (AChR) antibodies without clinical features of SLE or myasthenia gravis, suggesting a strong underlying autoimmune tendency. CT thorax showed no thymoma. Her symptoms improved with intravenous immunoglobulin infusion but recurred despite maintenance oral corticosteroids and carbamazepine. She has since been on regular IVIG infusions. Cold allodynia is an unusual presentation in acquired neuromyotonia.
Fulltext EEG is sensitive in early diagnosis of anti NMDAR encephalitis and useful in monitoring disease progress

Abdullah S, Lim KS, Wong WF, Tan HJ, Tan CT

Neurology Asia, 2015;20(2):167-175.
MyJurnal

Background& Objective: Investigation modalities, such as MRI and CSF examination, are neither sensitive nor specific in the early phase of anti-NMDAR encephalitis. Nuclear imaging may be useful to monitor the response to treatment but limited by the availability.We aimed to determine the role of EEG as a tool for early diagnosis as well as a tool to assess disease progression and response to treatment. Methods: A total of 99 EEGsdone in 16 patients diagnosed with anti-NMDAR encephalitis throughout the course of illness, were reviewed retrospectively. The EEG changes were correlated with the clinical presentations and response to treatment. Sixteen EEGs of patients with schizophrenia and mood disorder, and 10 EEGs of patients with infective encephalitis were included as control. Results: EEGs performed during the psychiatric and cognitive dysfunctionphase in patient with anti-NMDAR encephalitis, showed diffuse background slowing in the delta-theta range in all the patients. Serial EEGs showed that the dominant background frequency improved with improvement in cognitive status. Nine patients had complete recovery with normalisation of the EEG abnormalities. Eight patients had their typical clinical seizure recorded during EEG monitoring, but only 2 (25.0%) with EEG correlation. Ten patients had status epilepticus (62.5%), 5 had EEG recorded during their status epilepticus, of which only one with EEG correlation (20.0%). Eleven patients had asymmetric background (68.8%), but only 1 has correlation with focal changes in the MRI brain (9.1%). Even though the EEGs of patients with infective encephalitis also showed background slowing, their CSF analysis was supportive of an infective cause. EEGs of patients with established psychiatric disorder were within normal limits.
Conclusion: EEG abnormality has a good correlation with the degree of psychiatric and cognitive dysfunction in patient with anti-NMDAR encephalitis, and is useful in early diagnosis, monitoring the progress and the response to treatment. However, it has poor correlation with clinical seizures.
Insertion of single-chain variable fragment (scFv) peptide linker improves surface display of influenza hemagglutinin (HA1) on non-recombinant Lactococcus lactis

Jee PF, Chen FS, Shu MH, Wong WF, Abdul Rahim R, AbuBakar S, et al.

Biotechnol Prog, 2017 Jan;33(1):154-162.
PMID: 27802566 DOI: 10.1002/btpr.2400

Heterologous protein displayed on the surface of Lactococcus lactis using the binding domain of N-acetylmuramidase (AcmA) has a potential application in vaccine delivery. In this study, we developed a non-recombinant L. lactis surface displaying the influenza A (H1N1) 2009 hemagglutinin (HA1). Three recombinant proteins, HA1/L/AcmA, HA1/AcmA, and HA1 were overexpressed in Escherichia coli, and purified. In the binding study using flow cytometry, the HA1/L/AcmA, which contained the single-chain variable fragment (scFv) peptide linker showed significantly higher percentage of binding counts and mean fluorescence binding intensity (MFI) (51.7 ± 1.4% and 3,594.0 ± 675.9, respectively) in comparison to the HA1/AcmA without the scFv peptide linker (41.1 ± 1.5% and 1,652.0 ± 34.1, respectively). Higher amount of HA1/L/AcmA (∼2.9 × 10(4) molecules per cell) was displayed on L. lactis when compared to HA1/AcmA (∼1.1 × 10(4) molecules per cell) in the immunoblotting analysis. The HA1/L/AcmA completely agglutinated RBCs at comparable amount of protein to that of HA1/AcmA and HA1. Computational modeling of protein structures suggested that scFv peptide linker in HA1/L/AcmA kept the HA1 and the AcmA domain separated at a much longer distance in comparison to HA1/AcmA. These findings suggest that insertion of the scFv peptide linker between HA1 and AcmA improved binding of recombinant proteins to L. lactis. Hence, insertion of scFv peptide linker can be further investigated as a potential approach for improvement of heterologous proteins displayed on the surface of L. lactis using the AcmA binding domain. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:154-162, 2017.
Fulltext Transcriptomic and Genomic Approaches for Unravelling Candida albicans Biofilm Formation and Drug Resistance-An Update

Chong PP, Chin VK, Wong WF, Madhavan P, Yong VC, Looi CY

Genes (Basel), 2018 Nov 07;9(11).
PMID: 30405082 DOI: 10.3390/genes9110540

Candida albicans is an opportunistic fungal pathogen, which causes a plethora of superficial, as well as invasive, infections in humans. The ability of this fungus in switching from commensalism to active infection is attributed to its many virulence traits. Biofilm formation is a key process, which allows the fungus to adhere to and proliferate on medically implanted devices as well as host tissue and cause serious life-threatening infections. Biofilms are complex communities of filamentous and yeast cells surrounded by an extracellular matrix that confers an enhanced degree of resistance to antifungal drugs. Moreover, the extensive plasticity of the C. albicans genome has given this versatile fungus the added advantage of microevolution and adaptation to thrive within the unique environmental niches within the host. To combat these challenges in dealing with C. albicans infections, it is imperative that we target specifically the molecular pathways involved in biofilm formation as well as drug resistance. With the advent of the -omics era and whole genome sequencing platforms, novel pathways and genes involved in the pathogenesis of the fungus have been unraveled. Researchers have used a myriad of strategies including transcriptome analysis for C. albicans cells grown in different environments, whole genome sequencing of different strains, functional genomics approaches to identify critical regulatory genes, as well as comparative genomics analysis between C. albicans and its closely related, much less virulent relative, C. dubliniensis, in the quest to increase our understanding of the mechanisms underlying the success of C. albicans as a major fungal pathogen. This review attempts to summarize the most recent advancements in the field of biofilm and antifungal resistance research and offers suggestions for future directions in therapeutics development.
Nipah Virus Infection of Immature Dendritic Cells Increases Its Transendothelial Migration Across Human Brain Microvascular Endothelial Cells

Tiong V, Shu MH, Wong WF, AbuBakar S, Chang LY

Front Microbiol, 2018;9:2747.
PMID: 30483242 DOI: 10.3389/fmicb.2018.02747

Nipah virus (NiV) can infect multiple organs in humans with the central nervous system (CNS) being the most severely affected. Currently, it is not fully understood how NiV spreads throughout the body. NiV has been shown to infect certain leukocyte populations and we hypothesized that these infected cells could cross the blood-brain barrier (BBB), facilitating NiV entry into the CNS. Here, three leukocyte types, primary immature dendritic cells (iDC), primary monocytes (pMO), and monocytic cell line (THP-1), were evaluated for permissiveness to NiV. We found only iDC and THP-1 were permissive to NiV. Transendothelial migration of mock-infected and NiV-infected leukocytes was then evaluated using an in vitro BBB model established with human brain microvascular endothelial cells (HBMEC). There was approximately a threefold increase in migration of NiV-infected iDC across endothelial monolayer when compared to mock-infected iDC. In contrast, migration rates for pMO and THP-1 did not change upon NiV infection. Across TNF-α-treated endothelial monolayer, there was significant increase of almost twofold in migration of NiV-infected iDC and THP-1 over mock-infected cells. Immunofluorescence analysis showed the migrated NiV-infected leukocytes retained their ability to infect other cells. This study demonstrates for the first time that active NiV infection of iDC and THP-1 increased their transendothelial migration activity across HBMEC and activation of HBMEC by TNF-α further promoted migration. The findings suggest that NiV infection of leukocytes to disseminate the virus via the "Trojan horse" mechanism is a viable route of entry into the CNS.
Emerging frontiers of deep eutectic solvents in drug discovery and drug delivery systems

Zainal-Abidin MH, Hayyan M, Ngoh GC, Wong WF, Looi CY

J Control Release, 2019 12 28;316:168-195.
PMID: 31669211 DOI: 10.1016/j.jconrel.2019.09.019

The applications of eutectic systems, including deep eutectic solvents (DESs), in diverse sectors have drawn significant interest from researchers, academicians, engineers, medical scientists, and pharmacists. Eutecticity increases drug dissolution, improves drug penetration, and acts as a synthesis route for drug carriers. To date, DESs have been extensively explored as potential drug delivery systems on account of their unique properties such as tunability and chemical and thermal stability. This review discusses two major topics: first, the application of eutectic mixtures (before and after the introduction of DES) in the field of drug delivery systems, and second, the most promising examples of DES pharmaceutical activity. It also considers future prospects in the medical and biotechnological fields. In addition to the application of DESs in drug delivery systems, they show greatly promising pharmaceutical activities, including anti-fungal, anti-bacterial, anti-viral, and anti-cancer activities. Eutecticity is a valid strategy for overcoming many obstacles inherently associated with either introducing new drugs or enhancing drug delivery systems.
Fulltext The Microbiome and Irritable Bowel Syndrome - A Review on the Pathophysiology, Current Research and Future Therapy

Chong PP, Chin VK, Looi CY, Wong WF, Madhavan P, Yong VC

Front Microbiol, 2019;10:1136.
PMID: 31244784 DOI: 10.3389/fmicb.2019.01136

Irritable bowel syndrome (IBS) is a functional disorder which affects a large proportion of the population globally. The precise etiology of IBS is still unknown, although consensus understanding proposes IBS to be of multifactorial origin with yet undefined subtypes. Genetic and epigenetic factors, stress-related nervous and endocrine systems, immune dysregulation and the brain-gut axis seem to be contributing factors that predispose individuals to IBS. In addition to food hypersensitivity, toxins and adverse life events, chronic infections and dysbiotic gut microbiota have been suggested to trigger IBS symptoms in tandem with the predisposing factors. This review will summarize the pathophysiology of IBS and the role of gut microbiota in relation to IBS. Current methodologies for microbiome studies in IBS such as genome sequencing, metagenomics, culturomics and animal models will be discussed. The myriad of therapy options such as immunoglobulins (immune-based therapy), probiotics and prebiotics, dietary modifications including FODMAP restriction diet and gluten-free diet, as well as fecal transplantation will be reviewed. Finally this review will highlight future directions in IBS therapy research, including identification of new molecular targets, application of 3-D gut model, gut-on-a-chip and personalized therapy.
Fulltext Chronic Inflammatory Diseases at Secondary Sites Ensuing Urogenital or Pulmonary Chlamydia Infections

Cheok YY, Lee CYQ, Cheong HC, Looi CY, Wong WF

Microorganisms, 2020 Jan 17;8(1).
PMID: 31963395 DOI: 10.3390/microorganisms8010127

Chlamydia trachomatis and C. pneumoniae are members of the Chlamydiaceae family of obligate intracellular bacteria. The former causes diseases predominantly at the mucosal epithelial layer of the urogenital or eye, leading to pelvic inflammatory diseases or blindness; while the latter is a major causative agent for pulmonary infection. On top of these well-described diseases at the respective primary infection sites, Chlamydia are notoriously known to migrate and cause pathologies at remote sites of a host. One such example is the sexually acquired reactive arthritis that often occurs at few weeks after genital C. trachomatis infection. C. pneumoniae, on the other hand, has been implicated in an extensive list of chronic inflammatory diseases which include atherosclerosis, multiple sclerosis, Alzheimer's disease, asthma, and primary biliary cirrhosis. This review summarizes the Chlamydia infection associated diseases at the secondary sites of infection, and describes the potential mechanisms involved in the disease migration and pathogenesis.
Defining the Role of GLI/Hedgehog Signaling in Chemoresistance: Implications in Therapeutic Approaches

Chai JY, Sugumar V, Alshanon AF, Wong WF, Fung SY, Looi CY

Cancers (Basel), 2021 Sep 23;13(19).
PMID: 34638233 DOI: 10.3390/cancers13194746

Insight into cancer signaling pathways is vital in the development of new cancer treatments to improve treatment efficacy. A relatively new but essential developmental signaling pathway, namely Hedgehog (Hh), has recently emerged as a major mediator of cancer progression and chemoresistance. The evolutionary conserved Hh signaling pathway requires an in-depth understanding of the paradigm of Hh signaling transduction, which is fundamental to provide the necessary means for the design of novel tools for treating cancer related to aberrant Hh signaling. This review will focus substantially on the canonical Hh signaling and the treatment strategies employed in different studies, with special emphasis on the molecular mechanisms and combination treatment in regard to Hh inhibitors and chemotherapeutics. We discuss our views based on Hh signaling's role in regulating DNA repair machinery, autophagy, tumor microenvironment, drug inactivation, transporters, epithelial-to-mesenchymal transition, and cancer stem cells to promote chemoresistance. The understanding of this Achilles' Heel in cancer may improve the therapeutic outcome for cancer therapy.
Fulltext An Overview of Helicobacter pylori Survival Tactics in the Hostile Human Stomach Environment

Cheok YY, Lee CYQ, Cheong HC, Vadivelu J, Looi CY, Abdullah S, et al.

Microorganisms, 2021 Dec 03;9(12).
PMID: 34946105 DOI: 10.3390/microorganisms9122502

Helicobacter pylori is well established as a causative agent for gastritis, peptic ulcer, and gastric cancer. Armed with various inimitable virulence factors, this Gram-negative bacterium is one of few microorganisms that is capable of circumventing the harsh environment of the stomach. The unique spiral structure, flagella, and outer membrane proteins accelerate H. pylori movement within the viscous gastric mucosal layers while facilitating its attachment to the epithelial cells. Furthermore, secretion of urease from H. pylori eases the acidic pH within the stomach, thus creating a niche for bacteria survival and replication. Upon gaining a foothold in the gastric epithelial lining, bacterial protein CagA is injected into host cells through a type IV secretion system (T4SS), which together with VacA, damage the gastric epithelial cells. H. pylori does not only establishes colonization in the stomach, but also manipulates the host immune system to permit long-term persistence. Prolonged H. pylori infection causes chronic inflammation that precedes gastric cancer. The current review provides a brief outlook on H. pylori survival tactics, bacterial-host interaction and their importance in therapeutic intervention as well as vaccine development.
Paracrine IL-6 signaling mediates the effects of pancreatic stellate cells on epithelial-mesenchymal transition via Stat3/Nrf2 pathway in pancreatic cancer cells

Wu YS, Chung I, Wong WF, Masamune A, Sim MS, Looi CY

Biochim Biophys Acta Gen Subj, 2017 Feb;1861(2):296-306.
PMID: 27750041 DOI: 10.1016/j.bbagen.2016.10.006

BACKGROUND: We previously showed that pancreatic stellate cells (PSC) secreted interleukin (IL)-6 and promoted pancreatic ductal adenocarcinoma (PDAC) cell proliferation via nuclear factor erythroid 2 (Nrf2)-mediated metabolic reprogramming. Epithelial-mesenchymal transition (EMT) is a key process for the metastatic cascade. To study the mechanism of PDAC progression to metastasis, we investigated the role of PSC-secreted IL-6 in activating EMT and the involvement of Nrf2 in this process.
METHODS: Gene expression of IL-6 and IL-6Rα in PSC and PDAC cells was measured with qRT-PCR. The role of PSC-secreted IL-6, JAK/Stat3 signaling, and Nrf2 mediation on EMT-related genes expression was also examined with qRT-PCR. EMT phenotypes were assessed with morphological change, wound healing, migration, and invasion.
RESULTS: PSC expressed higher mRNA levels of IL-6 but lower IL-6Rα compared to PDAC cells. Neutralizing IL-6 in PSC secretion reduced mesenchymal-like morphology, migration and invasion capacity, and mesenchymal-like gene expression of N-cadherin, vimentin, fibronectin, collagen I, Sip1, Snail, Slug, and Twist2. Inhibition of JAK/Stat3 signaling induced by IL-6 repressed EMT and Nrf2 gene expression. Induction of Nrf2 activity by tert-butylhydroquinone (tBHQ) increased both EMT phenotypes and gene expression (N-cadherin, fibronectin, Twist2, Snail, and Slug) repressed by IL-6 neutralizing antibody. Simultaneous inhibition of Nrf2 expression with siRNA and Stat3 signaling further repressed EMT gene expression, indicating that Stat3/Nrf2 pathway mediates EMT induced by IL-6.
CONCLUSIONS: IL-6 from PSC promotes EMT in PDAC cells via Stat3/Nrf2 pathway.
GENERAL SIGNIFICANCE: Targeting Stat3/Nrf2 pathway activated by PSC-secreted IL-6 may provide a novel therapeutic option to improve the prognosis of PDAC.
Fulltext Unraveling the cytotoxicity and metabolic pathways of binary natural deep eutectic solvent systems

Mbous YP, Hayyan M, Wong WF, Looi CY, Hashim MA

Sci Rep, 2017 02 01;7:41257.
PMID: 28145498 DOI: 10.1038/srep41257

In this study, the anticancer potential and cytotoxicity of natural deep eutectic solvents (NADESs) were assessed using HelaS3, PC3, A375, AGS, MCF-7, and WRL-68 hepatic cell lines. NADESs were prepared from choline chloride, fructose, or glucose and compared with an N,N-diethyl ethanolammonium chloride:triethylene glycol DES. The NADESs (98 ≤ EC50 ≥ 516 mM) were less toxic than the DES (34 ≤ EC50 ≥ 120 mM). The EC50 values of the NADESs were significantly higher than those of the aqueous solutions of their individual components but were similar to those of the aqueous solutions of combinations of their chief elements. Due to the uniqueness of these results, the possibility that NADESs could be synthesized intracellularly to counterbalance the cytotoxicity of their excess principal constituents must be entertained. However, further research is needed to explore this avenue. NADESs exerted cytotoxicity by increasing membrane porosity and redox stress. In vivo, they were more destructive than the DES and induced liver failure. The potential of these mixtures was evidenced by their anticancer activity and intracellular processing. This infers that they can serve as tools for increasing our understanding of cell physiology and metabolism. It is likely that we only have begun to comprehend the nature of NADESs.
In vitro anti-oxidant and anti-cancer activity of methanolic extract from Sanchezia speciosa leaves

Paydar M, Wong YL, Moharam BA, Wong WF, Looi CY

Pak J Biol Sci, 2013 Oct 15;16(20):1212-5.
PMID: 24506026

Sanchezia speciosa, is a bushy shrub from Acanthaceae family which commonly grows in tropical areas of South and Central America. In this study, we employed MTT assay to test the cytotoxicity of that methanolic fraction of S. speciosa leaves on MCF-7 human breast cancer, SK-MEL-5 human malignant melanoma and human umbilical vein endothelial cells, HUVEC cells. The extract showed highest activity on MCF-7 and moderate cytotoxicity towards SK-MEL-5. In contrast, the extract demonstrated lowest cell growth inhibition activity on HUVEC cells, indicating better selectivity compare to standard drug, doxorubicin. In addition, we also performed ORAC assay to determine the radical scavenging capacity of methanolic extract of S. speciosa leaves. The extract exhibited nearly similar anti-oxidant activity as quercetin, suggesting S. speciosa leaves as a potential source of natural anti-oxidant. To the best of our knowledge, this is the first report on anti-oxidant and cytotoxic activity of S. speciosa.
Fulltext Natural deep eutectic solvents: cytotoxic profile

Hayyan M, Mbous YP, Looi CY, Wong WF, Hayyan A, Salleh Z, et al.

Springerplus, 2016;5(1):913.
PMID: 27386357 DOI: 10.1186/s40064-016-2575-9

The purpose of this study was to investigate the cytotoxic profiles of different ternary natural deep eutectic solvents (NADESs) containing water. For this purpose, five different NADESs were prepared using choline chloride as a salt, alongside five hydrogen bond donors (HBD) namely glucose, fructose, sucrose, glycerol, and malonic acid. Water was added as a tertiary component during the eutectics preparation, except for the malonic acid-based mixture. Coincidentally, the latter was found to be more toxic than any of the water-based NADESs. A trend was observed between the cellular requirements of cancer cells, the viscosity of the NADESs, and their cytotoxicity. This study also highlights the first time application of the conductor-like screening model for real solvent (COSMO-RS) software for the analysis of the cytotoxic mechanism of NADESs. COSMO-RS simulation of the interactions between NADESs and cellular membranes' phospholipids suggested that NADESs strongly interacted with cell surfaces and that their accumulation and aggregation possibly defined their cytotoxicity. This reinforced the idea that careful selection of NADESs components is necessary, as it becomes evident that organic acids as HBD highly contribute to the increasing toxicity of these neoteric mixtures. Nevertheless, NADESs in general seem to possess relatively less acute toxicity profiles than their DESs parents. This opens the door for future large scale utilization of these mixtures.
Fulltext Prevalence, antimicrobial susceptibility and virulotyping of Listeria species and Listeria monocytogenes isolated from open-air fish markets

Jamali H, Paydar M, Ismail S, Looi CY, Wong WF, Radmehr B, et al.

BMC Microbiol, 2015;15:144.
PMID: 26209099 DOI: 10.1186/s12866-015-0476-7

The aim of this study was to investigate the prevalence and characterization of Listeria species and Listeria monocytogenes isolated from raw fish and open-air fish market environments. Eight hundred and sixty two samples including raw fish and fish market environments (samples from workers' hands, workers' knives, containers and work surface) were collected from the open-air fish markets in the Northern region of Iran.
Fulltext Signal Transducer and Activator of Transcription (STATs) Proteins in Cancer and Inflammation: Functions and Therapeutic Implication

Loh CY, Arya A, Naema AF, Wong WF, Sethi G, Looi CY

Front Oncol, 2019;9:48.
PMID: 30847297 DOI: 10.3389/fonc.2019.00048

Signal Transducer and Activator of Transcription (STAT) pathway is connected upstream with Janus kinases (JAK) family protein and capable of integrating inputs from different signaling pathways. Each family member plays unique functions in signal transduction and crucial in mediating cellular responses to different kind of cytokines. STAT family members notably STAT3 and STAT5 have been involved in cancer progression whereas STAT1 plays opposite role by suppressing tumor growth. Persistent STAT3/5 activation is known to promote chronic inflammation, which increases susceptibility of healthy cells to carcinogenesis. Here, we review the role of STATs in cancers and inflammation while discussing current therapeutic implications in different cancers and test models, especially the delivery of STAT3/5 targeting siRNA using nanoparticulate delivery system.
β Mangostin suppress LPS-induced inflammatory response in RAW 264.7 macrophages in vitro and carrageenan-induced peritonitis in vivo

Syam S, Bustamam A, Abdullah R, Sukari MA, Hashim NM, Mohan S, et al.

J Ethnopharmacol, 2014 Apr 28;153(2):435-45.
PMID: 24607509 DOI: 10.1016/j.jep.2014.02.051

The fruit hull of Garcinia mangostana Linn. has been used in traditional medicine for treatment of various inflammatory diseases. Hence, this study aims to investigate the in vitro and in vivo anti-inflammatory effect of β mangostin (βM), a major compound present in Garcinia mangostana.
Fulltext Subditine, a new monoterpenoid indole alkaloid from bark of Nauclea subdita (Korth.) Steud. induces apoptosis in human prostate cancer cells

Liew SY, Looi CY, Paydar M, Cheah FK, Leong KH, Wong WF, et al.

PLoS One, 2014;9(2):e87286.
PMID: 24551054 DOI: 10.1371/journal.pone.0087286

In this study, a new apoptotic monoterpenoid indole alkaloid, subditine (1), and four known compounds were isolated from the bark of Nauclea subdita. Complete (1)H- and (13)C- NMR data of the new compound were reported. The structures of isolated compounds were elucidated with various spectroscopic methods such as 1D- and 2D- NMR, IR, UV and LCMS. All five compounds were screened for cytotoxic activities on LNCaP and PC-3 human prostate cancer cell-lines. Among the five compounds, the new alkaloid, subditine (1), demonstrated the most potent cell growth inhibition activity and selective against LNCaP with an IC50 of 12.24±0.19 µM and PC-3 with an IC50 of 13.97±0.32 µM, compared to RWPE human normal epithelial cell line (IC50 = 30.48±0.08 µM). Subditine (1) treatment induced apoptosis in LNCaP and PC-3 as evidenced by increased cell permeability, disruption of cytoskeletal structures and increased nuclear fragmentation. In addition, subditine (1) enhanced intracellular reactive oxygen species (ROS) production, as reflected by increased expression of glutathione reductase (GR) to scavenge damaging free radicals in both prostate cancer cell-lines. Excessive ROS could lead to disruption of mitochondrial membrane potential (MMP), release of cytochrome c and subsequent caspase 9, 3/7 activation. Further Western blot analyses showed subditine (1) induced down-regulation of Bcl-2 and Bcl-xl expression, whereas p53 was up-regulated in LNCaP (p53-wild-type), but not in PC-3 (p53-null). Overall, our data demonstrated that the new compound subditine (1) exerts anti-proliferative effect on LNCaP and PC-3 human prostate cancer cells through induction of apoptosis.
Fulltext Induction of apoptosis in melanoma A375 cells by a chloroform fraction of Centratherum anthelminticum (L.) seeds involves NF-kappaB, p53 and Bcl-2-controlled mitochondrial signaling pathways

Looi CY, Moharram B, Paydar M, Wong YL, Leong KH, Mohamad K, et al.

BMC Complement Altern Med, 2013;13:166.
PMID: 23837445 DOI: 10.1186/1472-6882-13-166

Centratherum anthelminticum (L.) Kuntze (scientific synonyms: Vernonia anthelmintica; black cumin) is one of the ingredients of an Ayurvedic preparation, called "Kayakalp", commonly applied to treat skin disorders in India and Southeast Asia. Despite its well known anti-inflammatory property on skin diseases, the anti-cancer effect of C. anthelminticum seeds on skin cancer is less documented. The present study aims to investigate the anti-cancer effect of Centratherum anthelminticum (L.) seeds chloroform fraction (CACF) on human melanoma cells and to elucidate the molecular mechanism involved.
Fulltext Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from Centratherum anthelminticum (L.) seeds

Looi CY, Arya A, Cheah FK, Muharram B, Leong KH, Mohamad K, et al.

PLoS One, 2013;8(2):e56643.
PMID: 23437193 DOI: 10.1371/journal.pone.0056643

Centratherum anthelminticum (L.) seeds (CA) is a well known medicinal herb in Indian sub-continent. We recently reported anti-oxidant property of chloroform fraction of Centratherum anthelminticum (L.) seeds (CACF) by inhibiting tumor necrosis factor-α (TNF-α)-induced growth of human breast cancer cells. However, the active compounds in CACF have not been investigated previously.

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