Displaying publications 61 - 80 of 107 in total

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  1. Lim KH, Lim HL, Teh CH, Kee CC, Heng PP, Cheah YK, et al.
    Tob Induc Dis, 2018;16.
    DOI: 10.18332/tid/95188
    Introduction: Understanding the prevalence of secondhand smoke (SHS) exposure and the associated factors is beneficial for the formulation of effective measures to reduce exposure to SHS. The purpose of this study was to determine SHS exposure at home and workplace, and its associated factors among non-smoker Malaysian adults. Methods: Data were extracted from the Global Adult Tobacco Survey-Malaysia (GATS-M) that involved a representative sample of 5112 Malaysian adults. Logistic regression analyses were performed to examine the association between SHS exposure, sociodemographic factors, knowledge on the danger of SHS, and smoking restrictions at home and at work among non-smokers. Results: Among non-smoker Malaysians, age ≥15 years, 27.9% (equivalent to approximately 4.21 million non-smokers) and 33.9% (equivalent to approximately 1.37 million non-smokers) reported that they were exposed to SHS at home and the workplace, at least once a month, respectively. Women (AOR=2.12, 95% CI: 1.61.2.78), young individuals (AOR=3.06, 95% CI: 1.48.6.33), Malays (AOR=2.39, 95% CI: 1.56.3.64) or other Bumiputra ethnic groups (AOR=2.40, 95% CI: 1.39.4.19) and those who worked as other than government employees were more likely to report SHS exposure at home (non-government employee: AOR=1.88, 95% CI: 1.06.3.36). Respondents with a total smoking restriction at home did not report any SHS exposure at home. Similarly, those whose workplace had smoking restrictions were less likely to report SHS exposure at the work compared to their counterparts whose workplace had partial (AOR=3.08, 95% CI: 1.84.5.15) or no smoking restrictions (AOR=15.33, 95% CI: 6.75.34.86). Conclusions: A substantial proportion of Malaysian adults were exposed to SHS at home and at work. The findings emphasize the need for policies on smoking restrictions at work and the need to promote the adoption of a completely smoke-free home, among the Malaysian population.
    Study name: Global Adults Tobacco Survey (GATS-2011)
  2. Ng SW, Selvarajah GT, Cheah YK, Mustaffa Kamal F, Omar AR
    Pathogens, 2020 May 25;9(5).
    PMID: 32466289 DOI: 10.3390/pathogens9050412
    Feline infectious peritonitis (FIP) is a fatal feline immune-mediated disease caused by feline infectious peritonitis virus (FIPV). Little is known about the biological pathways associated in FIP pathogenesis. This is the first study aiming to determine the phenotypic characteristics on the cellular level in relation to specific metabolic pathways of importance to FIP pathogenesis.

    METHODS: The internalization of type II FIPV WSU 79-1146 in Crandell-Rees Feline Kidney (CrFK) cells was visualized using a fluorescence microscope, and optimization prior to phenotype microarray (PM) study was performed. Then, four types of Biolog Phenotype MicroArray™ plates (PM-M1 to PM-M4) precoated with different carbon and nitrogen sources were used to determine the metabolic profiles in FIPV-infected cells.

    RESULTS: The utilization of palatinose was significantly low in FIPV-infected cells; however, there were significant increases in utilizing melibionic acid, L-glutamine, L-glutamic acid and alanyl-glutamine (Ala-Gln) compared to non-infected cells.

    CONCLUSION: This study has provided the first insights into the metabolic profiling of a feline coronavirus infection in vitro using PMs and deduced that glutamine metabolism is one of the essential metabolic pathways for FIPV infection and replication. Further studies are necessary to develop strategies to target the glutamine metabolic pathway in FIPV infection.

  3. Cheah YK, Syed Anera SN, Kee CC, Lim KH, Omar MA
    Hypertens Res, 2022 Feb 16.
    PMID: 35173284 DOI: 10.1038/s41440-022-00858-8
    The prevalence of high sodium-related diseases is increasing across the globe. Knowledge plays an important role in disease prevention. The objective of the present study was to examine sociodemographic factors associated with knowledge of high sodium-related diseases. The Malaysian Community Salt Survey (MyCoSS) was used in the present study for secondary analyses. It is a nationwide cross-sectional survey that was conducted in Malaysia. A non-parametric test to evaluate trends and a negative binomial regression were utilised to assess knowledge of high sodium-related diseases. Income, educational level, gender, ethnicity, house locality and hypertension were found to be significantly associated with knowledge of high sodium-related diseases. In particular, higher income earners, well-educated people, women, Malays, urban dwellers and hypertensive adults were more likely to have acquired a lot of knowledge of high sodium-related diseases compared to that acquired by lower income earners, less-educated people, men, individuals of other ethnic groups, rural dwellers and nonhypertensive adults. In conclusion, sociodemographic factors and hypertension play an important role in knowledge acquired about high sodium-related diseases. The findings of the present study could inform a future policy directed towards increasing knowledge about high sodium-related diseases among the population in Malaysia.
  4. Subha ST, Chin JW, Cheah YK, Mohtarrudin N, Saidi HI
    Mol Biol Rep, 2022 Feb;49(2):1501-1511.
    PMID: 34837627 DOI: 10.1007/s11033-021-06954-1
    MicroRNAs are small non-coding RNA that regulate gene expressions of human body. To date, numerous studies have reported that microRNAs possess great diagnostic and prognostic power in head and neck cancer and had governed a lot of attention. The factor for the successfulness of miRNAs in these aspects is due to cancer being fundamentally tied to genetic changes, which are regulated by these miRNAs. Head and neck cancer, leading the world record for cancer as number sixth, is caused by multiple risk factors such as tobacco consumption, alcohol consumption, dietary factors, ethnicity, family history, and human papilloma virus. It derives at locations such as oral cavity, pharynx, larynx, paranasal sinus and salivary gland and have high rate of mortality with high recurrence rate. Besides, head and neck cancer is also usually having poor prognosis due to its asymptomatic nature. However, this diagnostic and prognostic power can be further improved by using multiple panels of miRNA as a signature or even combined with TNM staging system to obtain even more remarkable results. This is due to multiple factors such as tumour heterogeneity and components of the tumour which may affect the composition of miRNAs. This review covers the examples of such miRNA signatures, compare their diagnostic and prognostic powers, discuss some controversial roles of unreported miRNAs, and the molecular mechanisms of the miRNAs in gene targeting and pathways.
  5. Sahabi K, Selvarajah GT, Abdullah R, Cheah YK, Tan GC
    J Vet Sci, 2018 Mar 31;19(2):162-171.
    PMID: 28927253 DOI: 10.4142/jvs.2018.19.2.162
    MicroRNAs (miRNAs) have important roles in all biological pathways in multicellular organisms. Over 1,400 human miRNAs have been identified, and many are conserved among vertebrates and invertebrates. Regulation of miRNA is the most common mode of post-transcriptional gene regulation. The miRNAs that are involved in the initiation and progression of cancers are termed oncomiRs and several of them have been identified in canine and human cancers. Similarly, several miRNAs have been reported to be down-regulated in cancers of the two species. In this review, current information on the expression and roles of miRNAs in oncogenesis and progression of human and canine cancers, as well the roles miRNAs have in cancer stem cell biology, are highlighted. The potential for the use of miRNAs as therapeutic targets in personalized cancer therapy in domestic dogs and their possible application in human cancer counterparts are also discussed.
  6. Cheah YK, Lim KK, Ismail H, Mohd Yusoff MF, Kee CC
    J Taibah Univ Med Sci, 2023 Aug;18(4):844-854.
    PMID: 36852251 DOI: 10.1016/j.jtumed.2022.12.016
    OBJECTIVES: Physical inactivity, hypertension and non-communicable diseases are major public concerns across the globe. To our knowledge, there is a lack of research that has investigated the moderating effect of age on the relationship between hypertension and physical activity in developing countries. This study had two objectives: (1) investigating hypertension and sociodemographic factors associated with physical activity and (2) investigating whether age moderates the relationship between hypertension and physical activity.

    METHODS: Nationally representative data of Malaysia were used to generate cross-sectional evidence. The sample size was 2156 respondents. An ordered probit regression was utilized to assess factors associated with the practice of physical activity.

    RESULTS: Respondents aged 40-49 years with hypertension were 7.3% less likely to participate in high-level physical activity when compared to those without hypertension. The probability of having a low level of physical activity was 12.3% higher among hypertensive patients aged ≥60. Males, married individuals, less-educated adults, low-income earners, and individuals who were aware of their BMI, had a higher tendency to indulge in a highly active lifestyle than others.

    CONCLUSION: The effect of hypertension on physical activity was moderated by age. Factors influencing physical activity levels among adults were income, gender, marital status, education, employment status, and BMI awareness.

  7. Teoh CP, Yusof NA, Budiman C, Cheah YK, Wong CMVL
    Data Brief, 2023 Jun;48:109052.
    PMID: 36942092 DOI: 10.1016/j.dib.2023.109052
    Arthrobacter is a coryneform bacterium in the family of Micrococcaceae. Arthrobacter species isolated from hostile environments are capable of producing interesting bioactive compounds, some of which may be a new class of antibiotics. Here, we present the complete genome sequence of Arthrobacter sp. ES1 isolated from Schirmacher Oasis in East Antarctica. Genomic DNA sequencing was performed using the Illumina MiSeq sequencer. Arthrobacter sp. ES1 has a genome size of 3,964,927 bp and a GC content of 65.73%. The raw genome sequences have been deposited in the NCBI Sequence Read Archive database under the accession number, SRR20664316.
  8. Cheah YK, Zainuddin NH, Kee CC, Lim KH, Omar MA, Cheong YL
    Clin Child Psychol Psychiatry, 2023 Oct;28(4):1341-1357.
    PMID: 36428238 DOI: 10.1177/13591045221142497
    Sexual behaviour and mental health among adolescents are major public health issues. This study examines how lifestyles affect sexual behaviour among school-going adolescents in Malaysia, and the potential mediational role of mental health. It is the first to our knowledge to explore the mediating effect of mental health on sexual behaviour with a focus on a fast-growing developing country. Data were obtained from the National Health and Morbidity Survey 2017 (n = 27,497). Structural equation modelling was utilized to examine depression and anxiety as mediators of the relationships between sexual behaviour and smoking, alcohol drinking and illicit drug use, controlling for sociodemographic factors. Results showed that adolescents who smoked, consumed alcohol, used illicit drugs, and had depression and anxiety were more likely to engage in sexual behaviour than others. Depression and anxiety partially mediated the relationships between sexual behaviour and smoking, and illicit drug use. The association between alcohol drinking and sexual behaviour was fully mediated by depression and anxiety. In conclusion, lifestyles may affect sexual behaviour through mediation of mental health. Therefore, policymakers should take mental health factors into consideration when designing adolescent sexual behaviour preventative interventions.
  9. Tan LK, Chua EH, Mohd Ghazali S, Cheah YK, Jayaraj VJ, Kee CC
    Nutrients, 2023 Dec 08;15(24).
    PMID: 38140302 DOI: 10.3390/nu15245043
    The healthy eating plate concept has been introduced in many countries, including Malaysia, as a visual guide for the public to eat healthily. The relationship between Malaysian Healthy Plate (MHP) and adequate fruit and vegetable (FV) intake among morbid Malaysian adults is unknown. Hence, we investigated the relationship between awareness of the MHP and FV intake among morbid Malaysian adults. National survey data on 9760 morbid Malaysian adults aged 18 years and above were analyzed. The relationship between awareness of MHP and FV intake among Malaysian adults with obesity, diabetes mellitus, hypertension, and hypercholesterolemia were determined using multivariable logistic regression controlling for sociodemographic characteristics and lifestyle risk factors. Our data demonstrated that MHP awareness is associated with adequate FV intake among the Malaysian adults with abdominal obesity (adjusted odds ratio (aOR): 1.86, 95% confidence interval (CI): 1.05-3.29), diabetes mellitus (aOR: 4.88, 95% CI: 2.13-22.18), hypertension (aOR: 4.39, 95% CI: 1.96-9.83), and hypercholesterolemia (aOR: 4.16, 95% CI: 1.48-11.72). Our findings indicated the necessity for ongoing efforts by policymakers, healthcare professionals, and nutrition educators to promote the concept of MHP and ensure that morbid Malaysian adults consume a sufficient intake of FV or adopt a healthy eating pattern to achieve and maintain optimal health.
  10. Foo JB, Yazan LS, Tor YS, Armania N, Ismail N, Imam MU, et al.
    PMID: 24947113 DOI: 10.1186/1472-6882-14-197
    Dillenia suffruticosa root dichloromethane extract (DCM-DS) has been reported to exhibit strong cytotoxicity towards breast cancer cells. The present study was designed to investigate the cell cycle profile, mode of cell death and signalling pathways of DCM-DS-treated human caspase-3 deficient MCF-7 breast cancer cells.
  11. Tor YS, Yazan LS, Foo JB, Armania N, Cheah YK, Abdullah R, et al.
    PMID: 24524627 DOI: 10.1186/1472-6882-14-55
    Breast cancer is one of the most dreading types of cancer among women. Herbal medicine has becoming a potential source of treatment for breast cancer. Herbal plant Dillenia suffruticosa (Griff) Martelli under the family Dilleniaceae has been traditionally used to treat cancerous growth. In this study, the anticancer effect of ethyl acetate extract of D. suffruticosa (EADs) was examined on human breast adenocarcinoma cell line MCF-7 and the molecular pathway involved was elucidated.
  12. Lee LH, Cheah YK, Sidik SM, Xie QY, Tang YL, Lin HP, et al.
    Int J Syst Evol Microbiol, 2013 Jan;63(Pt 1):241-248.
    PMID: 22389286 DOI: 10.1099/ijs.0.038232-0
    Three novel actinobacteria, strains 39(T), 40 and 41, were isolated from soil collected from Barrientos Island in the Antarctic. The taxonomic status of these strains was determined using a polyphasic approach. Comparison of 16S rRNA gene sequences revealed that strain 39(T) represented a novel lineage within the family Dermacoccaceae and was most closely related to members of the genera Demetria (96.9 % 16S rRNA gene sequence similarity), Branchiibius (95.7 %), Dermacoccus (94.4-95.3 %), Calidifontibacter (94.6 %), Luteipulveratus (94.3 %), Yimella (94.2 %) and Kytococcus (93.1 %). Cells were irregular cocci and short rods. The peptidoglycan type was A4α with an L-Lys-L-Ser-D-Asp interpeptide bridge. The cell-wall sugars were galactose and glucose. The major menaquinone was MK-8(H(4)). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphoglycolipid, two glycolipids and one unknown phospholipid. The acyl type of the cell-wall polysaccharide was N-acetyl. The major cellular fatty acids were anteiso-C(17 : 0) (41.97 %), anteiso-C(17 : 1)ω9c (32.16 %) and iso-C(16 : 0) (7.68 %). The DNA G+C content of strain 39(T) was 68.4 mol%. On the basis of phylogenetic and phenotypic differences from other genera of the family Dermacoccaceae, a novel genus and species, Barrientosiimonas humi gen. nov., sp. nov., is proposed; the type strain of the type species is 39(T) (=CGMCC 4.6864(T) = DSM 24617(T)).
  13. Lee LH, Cheah YK, Mohd Sidik S, Ab Mutalib NS, Tang YL, Lin HP, et al.
    World J Microbiol Biotechnol, 2012 May;28(5):2125-37.
    PMID: 22806035 DOI: 10.1007/s11274-012-1018-1
    The present study aimed to isolate actinobacteria from soil samples and characterized them using molecular tools and screened their secondary metabolites for antimicrobial activities. Thirty-nine strains from four different location of Barrientos Island, Antarctica using 12 types of isolation media was isolated. The isolates were preceded to screening of secondary metabolites for antimicrobial and antifungal activities. Using high-throughput screening methods, 38% (15/39) of isolates produced bioactive metabolites. Approximately 18% (7/39), 18% (7/39), 10% (4/39) and 2.5% (1/39) of isolates inhibited growth of Candida albicans ATCC 10231(T), Staphylococcus aurues ATCC 51650(T), methicillin-resistant Staphylococcus aurues (MRSA) ATCC BAA-44(T) and Pseudomonas aeruginosa ATCC 10145(T), respectively. Molecular characterization techniques like 16S rRNA analysis, Enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR), Random amplified polymorphic DNA (RAPD) and composite analyses were used to characterize the actinobacteria strains. Analysis of 16S rRNA sequences is still one of the most powerful methods to determine higher taxonomic relationships of Actinobacteria. Both RAPD and ERIC-PCR fingerprinting have shown good discriminatory capability but RAPD proved to be better in discriminatory power than ERIC-PCR. Our results demonstrated that composite analysis of both fingerprinting generally increased the discrimination ability and generated best clustering for actinobacteria strains in this study.
  14. Lee HY, Chai LC, Pui CF, Wong WC, Mustafa S, Cheah YK, et al.
    J Microbiol Biotechnol, 2011 Sep;21(9):954-9.
    PMID: 21952372
    There have been a number of studies conducted in order to compare the efficiencies of recovery rates, utilizing different protocols, for the isolation of L. monocytogenes. However, the severity of multiple cell injury has not been included in these studies. In the current study, L. monocytogenes ATCC 19112 was injured by exposure to extreme temperatures (60°C and -20°C) for a one-step injury, and for a two-step injury the cells were transferred directly from a heat treatment to frozen state to induce a severe cell injury (up to 100% injury). The injured cells were then subjected to the US Food and Drug Administration (FDA), the ISO-11290, and the modified United States Department of Agriculture (mUSDA) protocols, and plated on TSAyeast (0.6% yeast), PALCAM agar, and CHROMAgar Listeria for 24 h or 48 h. The evaluation of the total recovery of injured cells was also calculated based on the costs involved in the preparation of media for each protocol. Results indicate that the mUSDA method is best able to aid the recovery of heat-injured, freeze-injured, and heat-freeze-injured cells and was shown to be the most cost effective for heat-freeze-injured cells.
  15. Anarjan N, Tan CP, Ling TC, Lye KL, Malmiri HJ, Nehdi IA, et al.
    J Agric Food Chem, 2011 Aug 24;59(16):8733-41.
    PMID: 21726079 DOI: 10.1021/jf201314u
    A simplex centroid mixture design was used to study the interactions between two chosen solvents, dichloromethane (DCM) and acetone (ACT), as organic-phase components in the formation and physicochemical characterization and cellular uptake of astaxanthin nanodispersions produced using precipitation and condensation processes. Full cubic or quadratic regression models with acceptable determination coefficients were obtained for all of the studied responses. Multiple-response optimization predicted that the organic phase with 38% (w/w) DCM and 62% (w/w) ACT yielded astaxanthin nanodispersions with the minimum particle size (106 nm), polydispersity index (0.191), and total astaxanthin loss (12.7%, w/w) and the maximum cellular uptake (2981 fmol/cell). Astaxanthin cellular uptake from the produced nanodispersions also showed a good correlation with their particle size distributions and astaxanthin trans/cis isomerization ratios. The absence of significant (p > 0.05) differences between the experimental and predicted values of the response variables confirmed the adequacy of the fitted models.
  16. Tham CL, Lam KW, Rajajendram R, Cheah YK, Sulaiman MR, Lajis NH, et al.
    Eur J Pharmacol, 2011 Feb 10;652(1-3):136-44.
    PMID: 21114991 DOI: 10.1016/j.ejphar.2010.10.092
    We previously showed that 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC), suppressed the synthesis of various proinflammatory mediators. In this study we explain the mechanism of action of BHMC in lipopolysaccharide (LPS)-induced U937 monocytes and further show that BHMC prevents lethality of CLP-induced sepsis. BHMC showed dose-dependent inhibitory effects on p38, JNK and ERK 1/2 activity as determined by inhibition of phosphorylation of downstream transcription factors ATF-2, c-Jun and Elk-1 respectively. Inhibition of these transcription factors subsequently caused total abolishment of AP-1-DNA binding. BHMC inhibited p65 NF-κB nuclear translocation and DNA binding of p65 NF-κB only at the highest concentration used (12.5μM) but failed to alter phosphorylation of JNK, ERK1/2 and STAT-1. Since the inhibition of p38 activity was more pronounced we evaluated the possibility that BHMC may bind to p38. Molecular docking experiments confirmed that BHMC fits well in the highly conserved hydrophobic pocket of p38 MAP kinase. We also show that BHMC was able to improve survival from lethal sepsis in a murine caecal-ligation and puncture (CLP) model.
  17. Khoo CH, Cheah YK, Lee LH, Sim JH, Salleh NA, Sidik SM, et al.
    Antonie Van Leeuwenhoek, 2009 Nov;96(4):441-57.
    PMID: 19565351 DOI: 10.1007/s10482-009-9358-z
    The increased occurrence of Salmonella occurrence in local indigenous vegetables and poultry meat can be a potential health hazards. This study is aimed to detect the prevalence of twenty different virulence factors among Salmonella enterica strains isolated from poultry and local indigenous vegetables in Malaysia via an optimized, rapid and specific multiplex PCR assay. The assay encompasses a total of 19 Salmonella pathogenicity islands genes and a quorum sensing gene (sdiA) in three multiplex reaction sets. A total of 114 Salmonella enterica isolates belonging to 38 different serovars were tested. Each isolate in under this study was found to possess up to 70% of the virulence genes tested and exhibited variable pathogenicity gene patterns. Reproducibility of the multiplex PCR assay was found to be 100% and the detection limit of the optimized multiplex PCR was tested with lowest detectable concentration of DNA 0.8 pg microl(-1). This study demonstrated various Salmonella pathogenicity island virulence gene patterns even within the same serovar. This sets of multiplex PCR system provide a fast and reliable typing approach based on Salmonella pathogenicity islands, thus enabling an effective monitoring of emerging pathogenic Salmonella strains as an additional tool in Salmonella surveillance studies.
  18. Tan TB, Chu WC, Yussof NS, Abas F, Mirhosseini H, Cheah YK, et al.
    Food Funct, 2016 Apr 20;7(4):2043-51.
    PMID: 27010495 DOI: 10.1039/c5fo01621e
    In this study, we prepared a series of lutein nanodispersions via the solvent displacement method, by using surfactants with different stabilizing mechanisms. The surfactants used include Tween 80 (steric stabilization), sodium dodecyl sulfate (SDS; electrostatic stabilization), sodium caseinate (electrosteric stabilization) and SDS-Tween 80 (electrostatic-steric stabilization). We then characterized the resulting lutein nanodispersions in terms of their particle size, particle size distribution, zeta potential, lutein content, flow behavior, apparent viscosity, transmittance, color, morphological properties and their effects on cell viability and cellular uptake. The type of surfactant used significantly (p < 0.05) affected the physical properties of the nanodispersions, but the chemical properties (lutein content) remained unaffected. Transmission electron microscopy (TEM) images obtained from this study demonstrated that the solvent displacement method was capable of producing lutein nanodispersions containing spherical particles with sizes ranging from 66.20-125.25 nm, depending on the type of surfactant used. SDS and SDS-Tween 80 surfactants negatively affected the viability of the HT-29 cells used in this study. Thus, for the cellular uptake determination, only Tween 80 and sodium caseinate surfactants were used. The cellular uptake of the lutein nanodispersion stabilized by sodium caseinate was higher than that which was stabilized by Tween 80. All things considered, the type of surfactant with different stabilizing mechanisms did produce lutein nanodispersions with different characteristics. These findings would aid in future selection of surfactants in order to produce nanodispersions with desirable properties.
  19. Wan KF, Radu S, Cheah YK, Benjamin PG, Ling CM, Hon SF, et al.
    PMID: 15115139
    Enteropathogenic Escherichia coli (EPEC) is a leading cause of diarrhea among infants in developing countries. A total of 38 EPEC isolates, obtained from diarrhea patients of Hospital Miri, Sarawak, were investigated through plasmid profile, antibiotic resistance and randomly amplified polymorphic DNA (RAPD) analysis. From the 8 types of antibiotics used, all isolates were 100% resistant to furoxime, cephalothin and sulphamethoxazole and showed high multiple antibiotic resistant (MAR) indexes, ranging from 0.5 to 1.0. In plasmid profiling, 22 isolates (58%) showed the presence of one or more plasmids in the range 1.0 to 30.9 mDa. The dendrogram obtained from the results of the RAPD-PCR discriminated the isolates into 30 single isolates and 3 clusters at the level of 40% similarity. The EPEC isolates were highly diverse, as shown by their differing plasmid profiles, antibiotic resistance patterns and RAPD profiles.
  20. Ooi KK, Yeo CI, Mahandaran T, Ang KP, Akim AM, Cheah YK, et al.
    J Inorg Biochem, 2017 01;166:173-181.
    PMID: 27865929 DOI: 10.1016/j.jinorgbio.2016.11.008
    Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), were previously shown to be significantly cytotoxic toward HT-29 cancer cells and to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1 activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused apoptotic cell death via the c-Jun N-terminal kinase/mitogen-activated protein kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial cytochrome c measurements and annexin V screening, confirming apoptotic pathways of cell death. Cell cycle analysis showed the majority of treated HT-29 cells were arrested at the G2/M checkpoint after 24h; results of both assays were confirmed by changes in populations of relevant genes (PCR array analysis). Cell invasion studies showed inhibition of metastasis through Matrigel™ matrix to 17-22% cf. untreated cells. LC50values were determined in zebrafish (8.36, 8.17, and 7.64μM for 1-3). Finally, the zebrafish tolerated doses of 1 and 2 up to 0.625μM, and 3 was tolerated at even higher doses of up to 1.25μM.
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