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Fulltext Residual quantification and oxidative stress induced by malachite green after subacute and sublethal exposure in red tilapia

Kwan PP, Banerjee S, Shariff M, Yusoff FM

Vet World, 2019 Sep;12(9):1416-1421.
PMID: 31749575 DOI: 10.14202/vetworld.2019.1416-1421

Background and Aim: Malachite green (MG) is an effective antiparasitic and antifungal chemical for treatment of fish. However, MG is reported to be a potential carcinogen. Yet, it is widely used in aquaculture despite its prohibition for use in food-producing animals by the EU and USFDA. The present study quantified MG residues and evaluated the oxidative stress in red tilapia when exposed to subacute and sublethal concentrations of MG.
Materials and Methods: Red tilapia exposed to subacute (0.105 mg/L for 20 days) and sublethal (0.053 mg/L for 60 days) concentrations were evaluated for total plasma protein, total immunoglobulin, nitroblue tetrazolium activity, malondialdehyde, reduced glutathione (GSH), and catalase (CAT) activity levels. The residues of MG and leuco-MG (LMG) were also quantified in the fish muscles using liquid chromatography-tandem mass spectrometry.
Results: Fish exposed to subacute concentration showed higher CAT on day 10 in the liver and days 5 and 15 in the spleen, whereas in fish exposed to the sublethal concentration, higher levels of GSH were observed on day 1 in the kidney and day 50 in the spleen. Fish muscle was able to accumulate the sum of MG and LMG of 108.04 µg/kg for subacute (day 20) and 82.68 µg/kg for sublethal (day 60).
Conclusion: This study showed that red tilapia was able to adapt to the stress caused by exposure to MG at sublethal concentration.

Matched MeSH terms: Carcinogens
Fulltext Biochemical and molecular aspects of 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis: a review

Venkatachalam K, Vinayagam R, Arokia Vijaya Anand M, Isa NM, Ponnaiyan R

Toxicol Res (Camb), 2020 Feb;9(1):2-18.
PMID: 32440334 DOI: 10.1093/toxres/tfaa004

1,2-dimethylhydrazine (DMH) is a member in the class of hydrazines, strong DNA alkylating agent, naturally present in cycads. DMH is widely used as a carcinogen to induce colon cancer in animal models. Exploration of DMH-induced colon carcinogenesis in rodent models provides the knowledge to perceive the biochemical, molecular, and histological mechanisms of different stages of colon carcinogenesis. The procarcinogen DMH, after a series of metabolic reactions, finally reaches the colon, there produces the ultimate carcinogen and reactive oxygen species (ROS), which further alkylate the DNA and initiate the development of colon carcinogenesis. The preneolpastic lesions and histopathological observations of DMH-induced colon tumors may provide typical understanding about the disease in rodents and humans. In addition, this review discusses about the action of biotransformation and antioxidant enzymes involved in DMH intoxication. This understanding is essential to accurately identify and interpret alterations that occur in the colonic mucosa when evaluating natural or pharmacological compounds in DMH-induced animal colon carcinogenesis.

Matched MeSH terms: Carcinogens
Application of response surface methodology for the optimization of polycyclic aromatic hydrocarbons degradation from potable water using photo-Fenton oxidation process

Abd Manan TSB, Khan T, Sivapalan S, Jusoh H, Sapari N, Sarwono A, et al.

Sci Total Environ, 2019 May 15;665:196-212.
PMID: 30772550 DOI: 10.1016/j.scitotenv.2019.02.060

Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic compounds, composed of benzene rings. The objective of this research was to identify the optimum condition for the degradation of PAHs contaminated water using photo-Fenton oxidation process via response surface methodology (RSM). Aqueous solution was prepared and potable water samples were collected from water treatment plants in Perak Tengah, Perak, Malaysia in September 2016. The reaction time, pH, molarity of H2O2 and FeSO4 were analyzed followed by RSM using aqueous solution. A five level central composite design with quadratic model was used to evaluate the effects and interactions of these parameters. The response variable was the percentage of total organic carbon (TOC) removal. PAHs quantification was done using gas chromatography mass spectrometry analysis. The regression line fitted well with the data with R2 value of 0.9757. The lack of fit test gives the highest value of Sum of Squares (15,666.64) with probability F value 0.0001 showing significant quadratic model. The optimum conditions were established corresponding to the percentage of TOC removal. The PAHs removal efficiency for potable water samples ranged from 76.4% to 91% following the first order of kinetic rates with R2 values of >0.95. Conventional water treatment techniques are not effective for PAHs removal. Thus, advanced oxidation processes may be considered as an alternative to conventional water treatment techniques in Malaysia and other developing countries.

Matched MeSH terms: Carcinogens
Aflatoxins in unrefined groundnut oil

Chong YH, Beng CG

Med J Malaya, 1965 Sep;20(1):49-50.
PMID: 4221413
Matched MeSH terms: Carcinogens*
Fulltext FGFR3 mutation increases bladder tumourigenesis by suppressing acute inflammation

Foth M, Ismail NFB, Kung JSC, Tomlinson D, Knowles MA, Eriksson P, et al.

J Pathol, 2018 Nov;246(3):331-343.
PMID: 30043421 DOI: 10.1002/path.5143

Recent studies of muscle-invasive bladder cancer show that FGFR3 mutations are generally found in a luminal papillary tumour subtype that is characterised by better survival than other molecular subtypes. To better understand the role of FGFR3 in invasive bladder cancer, we examined the process of tumour development induced by the tobacco carcinogen OH-BBN in genetically engineered models that express mutationally activated FGFR3 S249C or FGFR3 K644E in the urothelium. Both occurrence and progression of OH-BBN-driven tumours were increased in the presence of an S249C mutation compared to wild-type control mice. Interestingly, at an early tumour initiation stage, the acute inflammatory response in OH-BBN-treated bladders was suppressed in the presence of an S249C mutation. However, at later stages of tumour progression, increased inflammation was observed in S249C tumours, long after the carcinogen administration had ceased. Early-phase neutrophil depletion using an anti-Ly6G monoclonal antibody resulted in an increased neutrophil-to-lymphocyte ratio at later stages of pathogenesis, indicative of enhanced tumour pathogenesis, which supports the hypothesis that suppression of acute inflammation could play a causative role. Statistical analyses of correlation showed that while initial bladder phenotypes in morphology and inflammation were FGFR3-dependent, increased levels of inflammation were associated with tumour progression at the later stage. This study provides a novel insight into the tumour-promoting effect of FGFR3 mutations via regulation of inflammation at the pre-tumour stage in the bladder. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Matched MeSH terms: Carcinogens
Vitamin E, glutathione S-transferase and gamma-glutamyl transpeptidase activities in cultured hepatocytes of rats treated with carcinogens

Ong FB, Wan Ngah WZ, Top AG, Khalid BA, Shamaan NA

Int. J. Biochem., 1994 Mar;26(3):397-402.
PMID: 7910569

1. The effects of alpha-tocopherol and gamma-tocotrienol on glutathione S-transferase (GST) and gamma-glutamyl transpeptidase (gamma-GT) activities in cultured hepatocytes prepared from rats treated with diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) were investigated. 2. Both the alpha-tocopherol and gamma-tocotrienol treated hepatocytes showed significantly higher (P < 0.05) GST activities than untreated hepatocytes prepared from the carcinogen treated rats in the first 3 days of culture. Treatment with alpha-tocopherol and gamma-tocotrienol generally resulted in a tendency to increase the GST activities above that in the untreated hepatocytes. 3. Treatment with high doses (125-250 microM) of alpha-tocopherol and low doses (12.5-25 microM) of gamma-tocotrienol generally resulted in a significant reduction in gamma-GT activities at 1-3 days. gamma-GT activities are reduced as the dose of alpha-tocopherol and gamma-tocotrienol are increased.

Matched MeSH terms: Carcinogens/toxicity*
Differential-based biosensor array for fluorescence-chemometric discrimination and the quantification of subtle chloropropanols by cross-reactive serum albumin scaffolding

Wong SF, Low KH, Khor SM

Talanta, 2020 Oct 01;218:121169.
PMID: 32797922 DOI: 10.1016/j.talanta.2020.121169

Food contamination is a serious concern because of a high level of chemicals in food causes severe health issues. Safeguarding the public from the risk of adulterated foods has become a challenging mission. Chloropropanols are of importance to food safety and food security because they are common chemical food contaminants and believed to be carcinogenic to humans. In chemical sensing, chloropropanols are challenging analytes owing to the lacking diversity of functional groups and difficulty in targeting the hydroxyl group in aqueous environments. Moreover, because of their small molecular size, the compositions of chloropropanols remain challenging for achieving chromatographic determination. Herein, to simulate human smell and taste sensations, serum albumins, which are protein-based receptors, were introduced as low-selective receptors for differential sensing. Utilizing serum albumins, a fluorophore (PRODAN), and an additive (ascorbic acid), a differential-based optical biosensor array was developed to detect and differentiate chloropropanols. By integrating the sensor array with linear discriminant analysis (LDA), four chloropropanols were effectively differentiated based on their isomerism properties and the number of the hydroxyl groups, even at ultra-low concentration (5 nM). This concentration is far below the maximum tolerable level of 0.18 μM for chloropropanols. The sensing array was then employed for chloropropanols differentiation and quantification in the complex mixtures (e.g., synthetic soy and dark soy sauces). Leave-one-out cross-validation (LOOCV) analysis demonstrated 100% accurate classification for all tests. These results signify our differential sensing array as a practical and powerful tool to speedily identify, differentiate, and even quantify chloropropanols in food matrices.

Matched MeSH terms: Carcinogens
Fulltext An Electrochemical DNA Biosensor for Carcinogenicity of Anticancer Compounds Based on Competition between Methylene Blue and Oligonucleotides

Md Sani ND, Ariffin EY, Sheryn W, Shamsuddin MA, Heng LY, Latip J, et al.

Sensors (Basel), 2019 Nov 22;19(23).
PMID: 31766637 DOI: 10.3390/s19235111

A toxicity electrochemical DNA biosensor has been constructed for the detection of carcinogens using 24 base guanine DNA rich single stranded DNA, and methylene blue (MB) as the electroactive indicator. This amine terminated ssDNA was immobilized onto silica nanospheres and deposited on gold nanoparticle modified carbon-paste screen printed electrodes (SPEs). The modified SPE was initially exposed to a carcinogen, followed by immersion in methylene blue for an optimized duration. The biosensor response was measured using differential pulse voltammetry. The performance of the biosensor was identified on several anti-cancer compounds. The toxicity DNA biosensor demonstrated a linear response range to the cadmium chloride from 0.0005 ppm to 0.01 ppm (R2 = 0.928) with a limit of detection at 0.0004 ppm. The biosensor also exhibited its versatility to screen the carcinogenicity of potential anti-cancer compounds.

Matched MeSH terms: Carcinogens/chemistry*
Fulltext Monitoring of heat-induced carcinogenic compounds (3-monochloropropane-1,2-diol esters and glycidyl esters) in fries

Wong YH, Goh KM, Nyam KL, Cheong LZ, Wang Y, Nehdi IA, et al.

Sci Rep, 2020 09 15;10(1):15110.
PMID: 32934328 DOI: 10.1038/s41598-020-72118-z

3-Monochloropropane-1,2-diol (3-MCPD) esters and glycidyl esters (GE) are heat-induced contaminants which form during oil refining process, particularly at the high temperature deodorization stage. It is worth to investigate the content of 3-MCPD and GE in fries which also involved high temperature. The content of 3-MCPD esters and GE were monitored in fries. The factors that been chosen were temperature and duration of frying, and different concentration of salt (NaCl). The results in our study showed that the effect was in the order of concentration of sodium chloride

Matched MeSH terms: Carcinogens/analysis*; Carcinogens/chemistry
Fulltext Health risk assessment and source apportionment of potentially toxic metal(loid)s in windowsill dust of a rapidly growing urban settlement, Iran

Madadi R, Mohamadi S, Rastegari M, Karbassi A, Rakib MRJ, Khandaker MU, et al.

Sci Rep, 2022 Nov 17;12(1):19736.
PMID: 36396803 DOI: 10.1038/s41598-022-21242-z

Rapid industrialization and urbanization have resulted in environmental pollution and unsustainable development of cities. The concentration of 12 potentially toxic metal(loid)s in windowsill dust samples (n = 50) were investigated from different functional areas of Qom city with the highest level of urbanization in Iran. Spatial analyses (ArcGIS 10.3) and multivariate statistics including Principal Component Analysis and Spearman correlation (using STATISTICA-V.12) were adopted to scrutinize the possible sources of pollution. The windowsill dust was very highly enriched with Sb (50 mg/kg) and Pb (1686 mg/kg). Modified degree of contamination (mCd) and the pollution load indices (PLIzone) indicate that windowsill dust in all functional areas was polluted in the order of industrial > commercial > residential > green space. Arsenic, Cd, Mo, Pb, Sb, Cu, and Zn were sourced from a mixture of traffic and industrial activities, while Mn in the dust mainly stemmed from mining activities. Non-carcinogenic health risk (HI) showed chronic exposure of Pb for children in the industrial zone (HI = 1.73). The estimations suggest the possible carcinogenic risk of As, Pb, and Cr in the dust. The findings of this study reveal poor environmental management of the city. Emergency plans should be developed to minimize the health risks of dust to residents.

Matched MeSH terms: Carcinogens/analysis
Fulltext Chemopreventive effects of Strobilanthes crispus leaf extract on azoxymethane-induced aberrant crypt foci in rat colon

Al-Henhena N, Khalifa SA, Ying RP, Hassandarvish P, Rouhollahi E, Al-Wajeeh NS, et al.

Sci Rep, 2015 Aug 26;5:13312.
PMID: 26307342 DOI: 10.1038/srep13312

In this work, microscopic and histological studies suggest that Strobilanthes crispus ethanol extract reduce azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. S. crispus is considered a traditional medicine and used as an antioxidant. Its leaf contains a large amount of phenolic compounds to which its radical scavenging role is attributed and enhance its ability to eradicate oxidative stress reactions. The study was designed to determine the chemopreventive effect of S. crispus ethanol extract in vivo and in vitro by elucidating the effect of the extract on intermediate biomarkers which can be used as effective predictors of colon cancer. S. crispus was analyzed for DPPH free radical scavenging, nitric oxide (NO) and ferric acid reduction. The results indicated that S. crispus oral administration significantly inhibited colorectal carcinogenesis induced by AOM as revealed by the reduction in the number of ACF. S. crispus down-regulated the expression of PCNA, Bcl2 and β-catenin. Additionally, it exerted a pronounced inhibitory effect on MDA and NO levels and stimulatory effect on CAT and GPx activities. These results demonstrate that S. crispus is a chemopreventive agent for colorectal cancer through the suppression of early and intermediate carcinogenic phases that may be related to its flavonoid content.

Matched MeSH terms: Carcinogens
Fulltext NTCU induced pre-malignant and malignant stages of lung squamous cell carcinoma in mice model

Zakaria MA, Rajab NF, Chua EW, Selvarajah GT, Masre SF

Sci Rep, 2021 Nov 18;11(1):22500.
PMID: 34795360 DOI: 10.1038/s41598-021-01988-8

Mice have served as an excellent model to understand the etiology of lung cancer for years. However, data regarding dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) remain elusive. Therefore, we aim to develop pre-malignant (PM) and malignant (M) lung SCC in vivo using N-nitroso-tris-chloroethylurea (NTCU). BALB/C mice were allotted into two main groups; PM and M groups which received treatment for 15 and 30 weeks, respectively. Then, the mice in each main group were allotted into three groups; control, vehicle, and cancer (n = 6), which received normal saline, 70% acetone, and 0.04 M NTCU by skin painting, respectively. Histopathologically, we discovered a mix of hyperplasia, metaplasia, and dysplasia lesions in the PM group and intracellular bridge; an SCC feature in the M group. The M group was positive for cytokeratin 5/6 protein which confirmed the lung SCC subtype. We also found significantly higher (P

Matched MeSH terms: Carcinogens
Mechanical and thermal properties of palm-based polyurethane composites filled with Fe3O4, PANI and PANI/Fe3O4

Liow CH, Sahrim Ahmad, Khairiah Badri

Sains Malaysiana, 2011;40.

In-situ polymerization method was used to prepare palm-based polyurethane (PU) composites loading with 15 wt% magnetite (Fe3O4), polyaniline (PANI) and Fe3O4 coated with PANI labeled as PU15, PP and PPM, respectively. FTIR spectroscopy analysis indicated a shift in the carbonyl, C=O and NH in PP. The shift of the peak indicated that there was hydrogen bonding between the C=O (proton acceptor) of urethane with NH (proton-donator) of PANI. PPM gave the highest impact and flexural strengths at 4875 kJ/ m2 and 42 MPa, respectively but with the lowest flexural modulus (1050 MPa). Two-stage degradation behavior was observed in the TGA thermogram.

Matched MeSH terms: Carcinogens
The effect of tocotrienol-rich fraction on the expression of glutathione s-transferase isoenzymes in mice liver

Ahmed Atia, Nadia Salem Alrawaiq, Azman Abdullah

Sains Malaysiana, 2018;47:2799-2809.

Glutathione S-transferase isoenzymes (GSTs) catalyze the conjugation reaction between glutathione and electrophilic
compounds. GSTs are involved in the detoxification of toxic and carcinogenic compounds, thus protecting the body from
toxic injuries. Tocotrienols are part of the vitamin E family and is believed to possess potent antioxidant activity. The
objective of this study was to determine the effect of increasing doses of tocotrienol rich fraction (TRF) supplementation
on liver GSTs gene and protein expression. A total of 30 male ICR white mice were divided into five groups (n=6 for each
group) and given treatment for 14 days through oral supplementation. Groups were divided as follows: - three groups
administered with TRF at doses of 200, 500 and 1000 mg/kg, respectively, a positive control group administered with 100
mg/kg butylated hydroxyanisole (BHA) and a control group administered with only the vehicle (corn oil). At day 15, the
mice were sacrificed and their livers isolated. Total RNA was extracted from the liver and quantitative real-time polymerase
chain reaction (qPCR) assays were performed to analyze GSTs gene expression. Total liver protein was also extracted
and the protein expression of GSTs was determined by Western blotting. The results showed that TRF oral supplementation
caused a significant dose-dependent increase in liver GST isoenzymes gene and protein expression, compared to controls.
In conclusion, TRF oral supplementation for 14 days resulted in increased gene and protein expression of GST isoenzymes
in mice liver dose-dependently, with the highest expression seen in mice treated with 1000 mg/kg TRF.

Matched MeSH terms: Carcinogens
Fulltext Chemopreventive evaluation of a Schiff base derived copper (II) complex against azoxymethane-induced colorectal cancer in rats

Hajrezaie M, Hassandarvish P, Moghadamtousi SZ, Gwaram NS, Golbabapour S, Najihussien A, et al.

PLoS One, 2014;9(3):e91246.
PMID: 24618844 DOI: 10.1371/journal.pone.0091246

Based on the potential of Schiff base compounds to act as sources for the development of cancer chemotherapeutic agents, this in vivo study was performed to investigate the inhibitory properties of the synthetic Schiff base compound Cu(BrHAP)2 on colonic aberrant crypt foci (ACF).

Matched MeSH terms: Carcinogens
Fulltext Sp1 and Sp3 Are the Transcription Activators of Human ek1 Promoter in TSA-Treated Human Colon Carcinoma Cells

Kuan CS, See Too WC, Few LL

PLoS One, 2016;11(1):e0147886.
PMID: 26807725 DOI: 10.1371/journal.pone.0147886

Ethanolamine kinase (EK) catalyzes the phosphorylation of ethanolamine, the first step in the CDP-ethanolamine pathway for the biosynthesis of phosphatidylethanolamine (PE). Human EK exists as EK1, EK2α and EK2β isoforms, encoded by two separate genes, named ek1 and ek2. EK activity is stimulated by carcinogens and oncogenes, suggesting the involvement of EK in carcinogenesis. Currently, little is known about EK transcriptional regulation by endogenous or exogenous signals, and the ek gene promoter has never been studied.

Matched MeSH terms: Carcinogens
Fulltext Health risk assessment among adult and children on potential air pollutants released from the petrochemical plant in Malaysia: the result of air modelling

Mohd Shahrol Abd Wahil, Wong, Chin Mun, Abdullah Aliff Abdul Wahab, Hasni Ja’afar

Pertanika Journal of Science & Technology, 2020;28(3):859-878.
MyJurnal

Malaysia is the world’s third largest exporter of liquified natural gas and the second largest oil and natural gas producer in Southeast Asia, following Indonesia. The potential air pollutants released from the industry may affect the health of the population. The primary objective of this study was to determine the potential health risk among the population in the zone of impact. This was a comparative case study between controlled and uncontrolled emissions based on the air dispersion modelling. Hazard quotient (HQ) was used to assess non-carcinogenic risk, while lifetime cancer risk (LCR) was used to assess carcinogenic risk. All ambient air pollutant levels were within permissible levels and adhered to the standard. The HQ for hydrogen sulphide and benzene was less than one in all scenarios. The LCR for benzene was acceptable in all scenarios. Advanced pollution prevention equipment should be installed within the gas emission system to treat the final emission to meet prescribed permissible limits. Continuous ambient air monitoring and effective control measures should be practiced to ensure the sustainability of clean air. The health risk assessment showed no risk of developing malignancy and non-cancer disorder among the workers and general population living surround the petrochemical plants. This allows the development of the petroleum refinery plants to be continued.

Matched MeSH terms: Carcinogens
Fulltext Deregulation of lysophosphatidic acid metabolism in oral cancer promotes cell migration via the up-regulation of COX-2

Abdul Rahman M, Tan ML, Johnson SP, Hollows RJ, Chai WL, Mansell JP, et al.

PeerJ, 2020;8:e10328.
PMID: 33240646 DOI: 10.7717/peerj.10328

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide and accounts for 300,000 new cases yearly. The five-year survival rate is approximately 50% and the major challenges to improving patient prognosis include late presentation, treatment resistance, second primary tumours and the lack of targeted therapies. Therefore, there is a compelling need to develop novel therapeutic strategies. In this study, we have examined the effect of lysophosphatidic acid (LPA) on OSCC cell migration, invasion and response to radiation, and investigated the contribution of cyclooxygenase-2 (COX-2) in mediating the tumour promoting effects of LPA. Using the TCGA data set, we show that the expression of the lipid phosphate phosphatases (LPP), LPP1 and LPP3, was significantly down-regulated in OSCC tissues. There was no significant difference in the expression of the ENPP2 gene, which encodes for the enzyme autotaxin (ATX) that produces LPA, between OSCCs and control tissues but ENPP2 levels were elevated in a subgroup of OSCCs. To explore the phenotypic effects of LPA, we treated OSCC cell lines with LPA and showed that the lipid enhanced migration and invasion as well as suppressed the response of the cells to irradiation. We also show that LPA increased COX-2 mRNA and protein levels in OSCC cell lines and inhibition of COX-2 activity with the COX-2 inhibitor, NS398, attenuated LPA-induced OSCC cell migration. Collectively, our data show for the first time that COX-2 mediates some of the pro-tumorigenic effects of LPA in OSCC and identifies the ATX-LPP-LPA-COX-2 pathway as a potential therapeutic target for this disease.

Matched MeSH terms: Carcinogens
Fulltext Brewers' Rice: A By-Product from Rice Processing Provides Natural Hepatorenal Protection in Azoxymethane-Induced Oxidative Stress in Rats

Tan BL, Norhaizan ME, Hairuszah I, Hazilawati H, Roselina K

Oxid Med Cell Longev, 2015;2015:539798.
PMID: 26257841 DOI: 10.1155/2015/539798

Brewers' rice, which is known locally as temukut, is a mixture of broken rice, rice bran, and rice germ. Our present study was designed to identify the effect of brewers' rice on the attenuation of liver and kidney damage induced by azoxymethane (AOM). Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), creatinine, and urea were evaluated to understand potential hepatoprotective effects and the ability of brewers' rice to attenuate kidney pathology induced by AOM treatment. Liver and kidney tissues were evaluated by hematoxylin and eosin (H&E) staining. Overall analyses revealed that brewers' rice improved the levels of serum markers in a manner associated with better histopathological outcomes, which indicated that brewers' rice could enhance recovery from hepatocyte and kidney damage. Taken together, these results suggest that brewers' rice could be used in future applications to combat liver and kidney disease.

Matched MeSH terms: Carcinogens/toxicity*
microRNA-548m suppresses cell migration and invasion by targeting aryl hydrocarbon receptor in breast cancer cells

Nor WMFSBW, Chung I, Said NABM

Oncol Res, 2020 Oct 27.
PMID: 33109304 DOI: 10.3727/096504020X16037933185170

Breast cancer is the most commonly diagnosed cancer among women and one of the leading causes of cancer mortality worldwide, in which the most severe form happens when it metastasizes to other regions of the body. Metastasis is responsible for most treatment failures in advanced breast cancer. Epithelial-mesenchymal transition (EMT) plays a significant role in promoting metastatic processes in breast cancer. MicroRNAs (miRNAs) are highly conserved endogenous short non-coding RNAs that play a role in regulating a broad range of biological processes, including cancer initiation and development, by functioning as tumor promoters or tumor suppressors. Expression of miR-548m has been found in various types of cancers, but the biological function and molecular mechanisms of miR-548m in cancers have not been fully studied. Here, we demonstrated the role of miR-548m in modulating EMT in the breast cancer cell lines MDA-MB-231 and MCF-7. Expression data for primary breast cancer obtained from NCBI GEO datasets showed that miR-548m expression was downregulated in breast cancer patients compared with healthy group. We hypothesize that miR-548m acts as a tumor suppressor in breast cancer. Overexpression of miR-548m in both cell lines increased E-cadherin expression and decreased the EMT-associated transcription factors SNAI1, SNAI2, ZEB1 and ZEB2, as well as MMP9 expression. Consequently, migration and invasion capabilities of both MDA-MB-231 and MCF-7 cells were significantly inhibited in miR-548m-overexpressing cells. Analysis of 1059 putative target genes of miR-548m revealed common pathways involving both tight junction and the mTOR signaling pathway, which has potential impacts on cell migration and invasion. Furthermore, this study identified aryl hydrocarbon receptor (AHR) as a direct target of miR-548m in breast cancer cells. Taken together, our findings suggest a novel function of miR-548m in reversing the EMT of breast cancer by reducing their migratory and invasive potentials, at least in part via targeting AHR expression.

Matched MeSH terms: Carcinogens

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