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AMD3100 protects from UV-induced skin cancer

Byrne SN, Sarchio SN

Oncoimmunology, 2014 Jan 01;3(1):e27562.
PMID: 24744978

Sunlight causes skin cancer by directly damaging DNA as well as by suppressing antitumor immune responses. A major mechanism whereby sunlight exerts immunosuppressive effects is by modulating the migration of chemokine (C-X-C motif) receptor 4 (CXCR4)-expressing dermal mast cells into and away from the skin. We have demonstrated the importance of this by showing that the systemic administration of the CXCR4 antagonist AMD3100 prevents sunlight-induced immunosuppression as well as the consequent carcinogenic response. Our results highlight the therapeutic potential of antagonizing CXCR4 signaling, especially in individuals who are at high risk of developing skin cancer.

Matched MeSH terms: Carcinogens
Dietary exposure to acrylamide among the Malaysian adult population

Nur Hidayah J, Abdul Razis AF, Jambari NN, Chai LC, You L, Sanny M

Food Chem Toxicol, 2024 Mar;185:114502.
PMID: 38346572 DOI: 10.1016/j.fct.2024.114502

This study aimed to estimate the Malaysian adult population's current dietary exposure and margin of exposure (MOE) to the carcinogenic processing contaminant, acrylamide. A total of 448 samples from 11 types of processed foods were collected randomly throughout Malaysia in the year 2015 and 2016. Acrylamide was analysed in samples using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) with a limit of detection (LOD) of 10 μg/kg and a limit of quantification (LOQ) of 25 μg/kg. The highest average level of acrylamide (772 ± 752 μg/kg) was found in potato crisps, followed by French fries (415 ± 914 μg/kg) and biscuits (245 ± 195 μg/kg). The total acrylamide exposure for the adult Malaysian was 0.229 and 1.77 μg/kg body weight per day for average and high consumers, respectively. The MOE were 741 and 1875 for the average consumer based on cancer and non-cancer effects of acrylamide, respectively. Meanwhile, for high consumers, the MOE is 96 for cancer and 243 for non-cancer effects. These findings indicate potential carcinogenic risks from acrylamide exposure among Malaysian adults, especially in Malay and other Bumiputra groups compared to Chinese, Indian, and other ethnic groups, while non-cancer effects appeared less concerning.

Matched MeSH terms: Carcinogens/analysis; Carcinogens/toxicity
Strobilanthes crispus attenuates renal carcinogen, iron nitrilotriacetate (Fe-NTA)-mediated oxidative damage of lipids and DNA

Iqbal M, Shah MD, Lie CA, San CK

Mol Cell Biochem, 2010 Aug;341(1-2):271-7.
PMID: 20376534 DOI: 10.1007/s11010-010-0458-x

This study was aimed to evaluate the effect of Strobilanthes crispus extract for possible protection against lipid peroxidation and DNA damage induced by iron nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H(2)O(2)). Fe-NTA is a potent nephrotoxic agent and induces acute and subacute renal proximal tubular necrosis by catalyzing the decomposition of H(2)O(2)-derived production of hydroxyl radicals, which are known to cause lipid peroxidation and DNA damage. Incubation of postmitochondrial supernatant and/or calf thymus DNA with H(2)O(2) (40 mM) in the presence of Fe-NTA (0.1 mM) induces lipid peroxidation and DNA damage to about 2.3-fold and 2.9-fold, respectively, as compared to control (P < 0.05). In lipid peroxidation protection studies, S. crispus treatment showed a dose-dependent inhibition (45-53% inhibition, P < 0.05) of Fe-NTA and H(2)O(2) induced lipid peroxidation. Similarly, in DNA damage protection studies, S. crispus treatment also showed a dose-dependent inhibition (18-30% inhibition, P < 0.05) of DNA damage. In addition, the protection was closely related to the content of phenolic compounds as evident by S. crispus extract showing the value of 124.48 mg/g total phenolics expressed as gallic acid equivalent (GAE, mg/g of extract). From these studies, it is concluded that S. crispus inhibits peroxidation of membrane lipids and DNA damage induced by Fe-NTA and H(2)O(2) and possesses the potential to be used to treat or prevent degenerative diseases where oxidative stress is implicated.

Matched MeSH terms: Carcinogens/toxicity
Fulltext Mitotic index and chromosomal analyses for hydroxyapatite implantation in rabbits

Kannan, T.P., Quah, B.B., Azlina, A., Samsudin, A.R.

Archives of Orofacial Sciences, 2006;1(1):15-20.
MyJurnal

Dentistry has searched for an ideal material to place in osseous defects for many years. Endogenous bone replacement has been the golden standard but involves additional surgery and may be available in limited quantities. Also, the exogenous bone replacement poses a risk of viral or bacterial transmission and the human body may even reject them. Therefore, before new biomaterials are approved for medical use, mutagenesis systems to exclude cytotoxic, mutagenic or carcinogenic properties are applied worldwide. The present preliminary study was carried out in five male New Zealand white rabbits (Oryctolagus cuniculus). Porous form of synthetic hydroxyapatite granules (500 mg), manufactured by School of Materials and Mineral Resources Engineering, Universiti Sains Malaysia, Penang, was implanted in the femur of the rabbits. Blood samples were collected prior to implantation and one week after implantation. The blood was cultured in vitro and the cell division was arrested at metaphase using colcemid. This was followed by the hypotonic treatment and fixation. Then, the chromosomes were prepared and stained for analysis. The modal chromosome number of rabbit (Oryctolagus cuniculus) was found to be 2n=44. The mean mitotic index values prior to and after implantation were 3.30 ± 0.66 and 3.24 ± 0.27 per cent respectively. No gross chromosome aberrations, both numerical and structural were noticed either prior to or after implantation of the biomaterial. These findings indicate that the test substance, synthetic hydroxyapatite granules does not produce gross chromosome aberrations under the present test conditions in rabbits.

Matched MeSH terms: Carcinogens
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
Fulltext Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?

Robey RB, Weisz J, Kuemmerle NB, Salzberg AC, Berg A, Brown DG, et al.

Carcinogenesis, 2015 Jun;36 Suppl 1(Suppl 1):S203-31.
PMID: 26106140 DOI: 10.1093/carcin/bgv037

Environmental contributions to cancer development are widely accepted, but only a fraction of all pertinent exposures have probably been identified. Traditional toxicological approaches to the problem have largely focused on the effects of individual agents at singular endpoints. As such, they have incompletely addressed both the pro-carcinogenic contributions of environmentally relevant low-dose chemical mixtures and the fact that exposures can influence multiple cancer-associated endpoints over varying timescales. Of these endpoints, dysregulated metabolism is one of the most common and recognizable features of cancer, but its specific roles in exposure-associated cancer development remain poorly understood. Most studies have focused on discrete aspects of cancer metabolism and have incompletely considered both its dynamic integrated nature and the complex controlling influences of substrate availability, external trophic signals and environmental conditions. Emerging high throughput approaches to environmental risk assessment also do not directly address the metabolic causes or consequences of changes in gene expression. As such, there is a compelling need to establish common or complementary frameworks for further exploration that experimentally and conceptually consider the gestalt of cancer metabolism and its causal relationships to both carcinogenesis and the development of other cancer hallmarks. A literature review to identify environmentally relevant exposures unambiguously linked to both cancer development and dysregulated metabolism suggests major gaps in our understanding of exposure-associated carcinogenesis and metabolic reprogramming. Although limited evidence exists to support primary causal roles for metabolism in carcinogenesis, the universality of altered cancer metabolism underscores its fundamental biological importance, and multiple pleiomorphic, even dichotomous, roles for metabolism in promoting, antagonizing or otherwise enabling the development and selection of cancer are suggested.

Matched MeSH terms: Carcinogens, Environmental/adverse effects*
Fulltext Environmental influence and intention to quit smoking among college students

Muhammad Adil Zainal Abidin, Hayati Kadir Shahar, Rosliza Abdul Manaf

Malaysian Journal of Medicine and Health Sciences, 2019;15(104):77-77.
MyJurnal

Introduction: Secondhand tobacco smoke is a known carcinogen and has shown positive association with smok-ing status, susceptibility and cessation. Smoke free environment policy seem to reduce this exposure and influence intention to quit and frequency of quit attempts. Despite having a smoke free policy, smokers are still exposed to second hand smoke and this might influence their smoking behaviour and cessation. The objective of this study was to examine the association between environmental tobacco smoke exposures with intention to quit smoking among young adults in college with smoke free policy. Methods: Data were drawn from a cluster based randomised controlled trial in 10 government colleges in Selangor. Baseline characteristics of 160 college smokers were mea-sured using adapted questionnaire. Intention to quit was measured using Transtheoretical Model and environmental influence of tobacco smoke exposure. Results: Majority of the smokers were male (99.4%), single (100%), of Malay ethnicity (94.4%) and Muslim (95.6%). Most of them are in pre-contemplation stage where they do not have any intention to quit (65.6%). On environmental influence, at work or college environmental exposure, majority were exposed between 1 to 2 hours (36.9%) and 3 to 8 hours (40.6%). On exposure at home or hostel, majority were exposed between 1 to 4 hours (44.4%) and 5 to 14 hours (21.9%). In terms of friend’s exposures, majority have most of their friends smoking (68.1%). We found no statistically significant association between environmental influence and intention to quit smoking. Conclusion: Although we found no relationship, future research should examine the pathway between environmental influence and smoking behaviour.

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*
Genetic, epigenetic, and lineage-directed mechanisms in benzene-induced malignancies and hematotoxicity targeting hematopoietic stem cells niche

Dewi R, Hamid ZA, Rajab NF, Shuib S, Razak SA

Hum Exp Toxicol, 2020 May;39(5):577-595.
PMID: 31884827 DOI: 10.1177/0960327119895570

Benzene is a known hematotoxic and leukemogenic agent with hematopoietic stem cells (HSCs) niche being the potential target. Occupational and environmental exposure to benzene has been linked to the incidences of hematological disorders and malignancies. Previous studies have shown that benzene may act via multiple modes of action targeting HSCs niche, which include induction of chromosomal and micro RNA aberrations, leading to genetic and epigenetic modification of stem cells and probable carcinogenesis. However, understanding the mechanism linking benzene to the HSCs niche dysregulation is challenging due to complexity of its microenvironment. The niche is known to comprise of cell populations accounted for HSCs and their committed progenitors of lymphoid, erythroid, and myeloid lineages. Thus, it is fundamental to address novel approaches via lineage-directed strategy to elucidate precise mechanism involved in benzene-induced toxicity targeting HSCs and progenitors of different lineages. Here, we review the key genetic and epigenetic factors that mediate hematotoxicological effects by benzene and its metabolites in targeting HSCs niche. Overall, the use of combined genetic, epigenetic, and lineage-directed strategies targeting the HSCs niche is fundamental to uncover the key mechanisms in benzene-induced hematological disorders and malignancies.

Matched MeSH terms: Carcinogens/pharmacokinetics; Carcinogens/toxicity*
Biomedical Applications of Aromatic Azo Compounds

Ali Y, Hamid SA, Rashid U

Mini Rev Med Chem, 2018;18(18):1548-1558.
PMID: 29792144 DOI: 10.2174/1389557518666180524113111

Azo dyes are widely used in textile, fiber, cosmetic, leather, paint and printing industries. Besides their characteristic coloring function, azo compounds are reported as antibacterial, antiviral, antifungal and cytotoxic agents. They have the ability to be used as drug carriers, either by acting as a 'cargo' that entrap therapeutic agents or by prodrug approach. The drug is released by internal or external stimuli in the region of interest, as observed in colon-targeted drug delivery. Besides drug-like and drug carrier properties, a number of azo dyes are used in cellular staining to visualize cellular components and metabolic processes. However, the biological significance of azo compounds, especially in cancer chemotherapy, is still in its infancy. This may be linked to early findings that declared azo compounds as one of the possible causes of cancer and mutagenesis. Currently, researchers are screening the aromatic azo compounds for their potential biomedical use, including cancer diagnosis and therapy. In this review, we highlight the medical applications of azo compounds, particularly related to cancer research. The biomedical significance of cis-trans interchange and negative implications of azo compounds are also discussed in brief.

Matched MeSH terms: Carcinogens/toxicity
Fulltext Proximate analysis, mineral content and antioxidant capacity of milk apple, malay apple and water apple

Lim, A.S.L., Rabeta, M.S.

International Food Research Journal, 2013;20(2):673-679.
MyJurnal

The aim of this study is to determine the antioxidant capacity of underutilized fruits in Malaysia namely Milk apple (Syzygium malaccense), Malay apple (Syzygium malaccense (L.) Merr. and Perry), and Water apple (Syzygium aqueum). Synthetic antioxidants (BHA and BHT) commonly used in the food industries may not be as safe as it was presumed earlier. As BHA and BHT may be carcinogenic, it is important to look for new sources of natural antioxidants from fruits and vegetables. Freeze dried samples extracted with acetone and water were measured by ferric 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and Ferric Reducing Antioxidant Power (FRAP) assays. Acetone extract (50%) showed higher values for both DPPH and FRAP assays compared with water extract. Milk apple has the highest DPPH value of 95.26% inhibition of DPPH. Milk apple also showed the highest FRAP value with 8722.22 µM of Fe (II) per gram of freeze dried sample. There was a significant difference (P < 0.05) in the types of extraction used. Antioxidant capacities of the samples are in the following order: Milk apple > Malay apple > Water apple. Proximate compositions and mineral contents of the samples were determined too. The samples can be used as a source of natural antioxidants.

Matched MeSH terms: Carcinogens
Is There an Association Between Ambient Air Pollution and Bladder Cancer Incidence? Analysis of 15 European Cohorts

Pedersen M, Stafoggia M, Weinmayr G, Andersen ZJ, Galassi C, Sommar J, et al.

Eur Urol Focus, 2018 01;4(1):113-120.
PMID: 28753823 DOI: 10.1016/j.euf.2016.11.008

BACKGROUND: Ambient air pollution contains low concentrations of carcinogens implicated in the etiology of urinary bladder cancer (BC). Little is known about whether exposure to air pollution influences BC in the general population.
OBJECTIVE: To evaluate the association between long-term exposure to ambient air pollution and BC incidence.
DESIGN, SETTING, AND PARTICIPANTS: We obtained data from 15 population-based cohorts enrolled between 1985 and 2005 in eight European countries (N=303431; mean follow-up 14.1 yr). We estimated exposure to nitrogen oxides (NO2 and NOx), particulate matter (PM) with diameter <10μm (PM10), <2.5μm (PM2.5), between 2.5 and 10μm (PM2.5-10), PM2.5absorbance (soot), elemental constituents of PM, organic carbon, and traffic density at baseline home addresses using standardized land-use regression models from the European Study of Cohorts for Air Pollution Effects project.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used Cox proportional-hazards models with adjustment for potential confounders for cohort-specific analyses and meta-analyses to estimate summary hazard ratios (HRs) for BC incidence.
RESULTS AND LIMITATIONS: During follow-up, 943 incident BC cases were diagnosed. In the meta-analysis, none of the exposures were associated with BC risk. The summary HRs associated with a 10-μg/m3 increase in NO2 and 5-μg/m3 increase in PM2.5 were 0.98 (95% confidence interval [CI] 0.89-1.08) and 0.86 (95% CI 0.63-1.18), respectively. Limitations include the lack of information about lifetime exposure.
CONCLUSIONS: There was no evidence of an association between exposure to outdoor air pollution levels at place of residence and risk of BC.
PATIENT SUMMARY: We assessed the link between outdoor air pollution at place of residence and bladder cancer using the largest study population to date and extensive assessment of exposure and comprehensive data on personal risk factors such as smoking. We found no association between the levels of outdoor air pollution at place of residence and bladder cancer risk.

Matched MeSH terms: Carcinogens, Environmental/adverse effects*
Predicting points of departure for risk assessment based on in vitro cytotoxicity data and physiologically based kinetic (PBK) modeling: The case of kidney toxicity induced by aristolochic acid I

Abdullah R, Alhusainy W, Woutersen J, Rietjens IM, Punt A

Food Chem Toxicol, 2016 Jun;92:104-16.
PMID: 27016491 DOI: 10.1016/j.fct.2016.03.017

Aristolochic acids are naturally occurring nephrotoxins. This study aims to investigate whether physiologically based kinetic (PBK) model-based reverse dosimetry could convert in vitro concentration-response curves of aristolochic acid I (AAI) to in vivo dose response-curves for nephrotoxicity in rat, mouse and human. To achieve this extrapolation, PBK models were developed for AAI in these different species. Subsequently, concentration-response curves obtained from in vitro cytotoxicity models were translated to in vivo dose-response curves using PBK model-based reverse dosimetry. From the predicted in vivo dose-response curves, points of departure (PODs) for risk assessment could be derived. The PBK models elucidated species differences in the kinetics of AAI with the overall catalytic efficiency for metabolic conversion of AAI to aristolochic acid Ia (AAIa) being 2-fold higher for rat and 64-fold higher for mouse than human. Results show that the predicted PODs generally fall within the range of PODs derived from the available in vivo studies. This study provides proof of principle for a new method to predict a POD for in vivo nephrotoxicity by integrating in vitro toxicity testing with in silico PBK model-based reverse dosimetry.

Matched MeSH terms: Carcinogens/toxicity*
Characterization and Risk Analysis of Metals Associated with Urban Dust in Rawang (Malaysia)

Praveena SM

Arch Environ Contam Toxicol, 2018 Oct;75(3):415-423.
PMID: 29802419 DOI: 10.1007/s00244-018-0537-7

This study was designed to determine the particle size distribution and develop road dust index combining source and transport factors involving road dust for dust pollution quantification in Rawang. Principal component analysis (PCA) was applied to identify possible sources of potentially toxic elements and spot major pollution areas in Rawang. The health risks (carcinogenic and noncarcinogenic) to adults and children were assessed using the hazard index and total lifetime cancer Risk, respectively. A total of 75 road dust samples were collected and particle sizes (1000, 500, 250, 160, 125 and 63 µm) were determined. Concentrations of potentially toxic elements (Cu, Cd, Co, Cr, Pb, Ni, Zn and As) in particle size of 63 µm were analyzed. The results demonstrated that the highest grain size of 250 µm has contributed almost more than 25% of atmospheric particulate pollution. The highest potentially toxic element concentration was Pb (593.3 mg/kg), whereas the lowest was Co (5.6 mg/kg). Road dust index output indicated that pollution risk fell into moderate levels in eastern and northern areas of Rawang. Similarly, PCA results revealed that potentially toxic elements (Cu, Cd, Pb, Zn, Ni and Cr) were linked with anthropogenic sources (urbanization process, industrial and commercial growth, urban traffic congestion) in northern and southern parts of Rawang. Cobalt and As concentrations were explained mainly from natural sources. Noncarcinogenic risk by hazard index value more than 1.0 was indicated for adults and children. Similarly, carcinogenic risk by total lifetime cancer risk value also showed carcinogenic risks among adults and children.

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
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 Disruptive environmental chemicals and cellular mechanisms that confer resistance to cell death

Narayanan KB, Ali M, Barclay BJ, Cheng QS, D'Abronzo L, Dornetshuber-Fleiss R, et al.

Carcinogenesis, 2015 Jun;36 Suppl 1:S89-110.
PMID: 26106145 DOI: 10.1093/carcin/bgv032

Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental carcinogenesis.

Matched MeSH terms: Carcinogens, Environmental/adverse effects*
Inhibitory effects of Tualang Honey on experimental breast cancer in rats: a preliminary study

Kadir EA, Sulaiman SA, Yahya NK, Othman NH

Asian Pac J Cancer Prev, 2013;14(4):2249-54.
PMID: 23725121

The study was conducted to determine the effect of Malaysian jungle Tualang Honey (TH) on development of breast cancer induced by the carcinogen 7,12-dimethylbenz(α)anthracene (DMBA) in rats. Forty nulliparous female Sprague-Dawley rats were given 80 mg/kg DMBA then randomly divided into four groups: Group 1 served as a Control while Groups 2, 3 and 4 received 0.2, 1.0 or 2.0 g/kg bodyweight/day of TH, respectively, for 150 days. Results showed that breast cancers in the TH-treated groups had slower size increment and smaller mean tumor size (≤ 2 cm3) compared to Controls (≤ 8 cm3). The number of cancers developing in TH-treated groups was also significantly fewer (P<0.05). Histological grading showed majority of TH-treated group cancers to be of grade 1 and 2 compared to grade 3 in controls. There was an increasing trend of apoptotic index (AI) seen in TH-treated groups with increasing dosage of Tualang Honey, however, the mean AI values of all TH-treated groups were not significantly different from the Control value (p>0.05). In conclusion, Tualang Honey exerted positive modulation effects on DMBA-induced breast cancers in rats in this preliminary study.

Matched MeSH terms: Carcinogens/toxicity
Fulltext The therapeutic potential of curcumin in alleviating N-diethylnitrosamine and iron nitrilotriacetate induced renal cell tumours in mice via inhibition of oxidative stress: Implications for cancer chemoprevention

Iqbal M, Shah MD, Vun-Sang S, Okazaki Y, Okada S

Biomed Pharmacother, 2021 Jul;139:111636.
PMID: 33957566 DOI: 10.1016/j.biopha.2021.111636

This study was designed to reveal the protective effects of dietary supplementation of curcumin against renal cell tumours and oxidative stress induced by renal carcinogen iron nitrilotriacetate (Fe-NTA) in ddY male mice. The results showed that mice treated with a renal carcinogen, Fe-NTA, a 35% renal cell tumour incidence was noticed, whereas renal cell tumour occurrence was elevated to 80% in Fe-NTA promoted and N-diethylnitrosamine (DEN)-initiated mice as compared with saline- treated mice. No incidence of tumours has been observed in DEN-initiated non-promoted mice. Diet complemented with 0.5% and 1.0% curcumin fed prior to, during and after treatment with Fe-NTA in DEN-initiated animals, tumour incidence was reduced dose-dependently to about 45% and 30% respectively. Immunohistochemical studies also revealed the increased formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in kidney tissue of mice treated with an intraperitoneal injection of Fe-NTA (6.0 mg Fe/kg body weight.). Furthermore, Fe-NTA treatment of mice also resulted in significant elevation of malondialdehyde (MDA), serum urea, and creatinine and decreases renal glutathione. However, the changes in most of these parameters were attenuated dose-dependently by prophylactic treatment of animals with 0.5% and 1% curcumin diet, this may be due to its antioxidative impact of curcumin. These results suggest that intake of curcumin is beneficial for the prevention of renal cell tumours and oxidative stress damage mediated by renal carcinogen, Fe-NTA.

Matched MeSH terms: Carcinogens
Curcumin attenuates oxidative damage in animals treated with a renal carcinogen, ferric nitrilotriacetate (Fe-NTA): implications for cancer prevention

Iqbal M, Okazaki Y, Okada S

Mol Cell Biochem, 2009 Apr;324(1-2):157-64.
PMID: 19165575 DOI: 10.1007/s11010-008-9994-z

Curcumin (diferuloylmethane), a biologically active ingredient derived from rhizome of the plant Curcuma longa, has potent anticancer properties as demonstrated in a plethora of human cancer cell lines/animal carcinogenesis model and also acts as a biological response modifier in various disorders. We have reported previously that dietary supplementation of curcumin suppresses renal ornithine decarboxylase (Okazaki et al. Biochim Biophys Acta 1740:357-366, 2005) and enhances activities of antioxidant and phase II metabolizing enzymes in mice (Iqbal et al. Pharmacol Toxicol 92:33-38, 2003) and also inhibits Fe-NTA-induced oxidative injury of lipids and DNA in vitro (Iqbal et al. Teratog Carcinog Mutagen 1:151-160, 2003). This study was designed to examine whether curcumin possess the potential to suppress the oxidative damage caused by kidney-specific carcinogen, Fe-NTA, in animals. In accord with previous report, at 1 h after Fe-NTA treatment (9.0 mg Fe/kg body weight intraperitoneally), a substantial increased formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts in renal proximal tubules of animals was observed. Likewise, the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and protein reactive carbonyl, an indicator of protein oxidation, were also increased at 1 h after Fe-NTA treatment in the kidneys of animals. The prophylactic feeding of animals with 1.0% curcumin in diet for 4 weeks completely abolished the formation of (i) HNE-modified protein adducts, (ii) 8-OHdG, and (iii) protein reactive carbonyl in the kidneys of Fe-NTA-treated animals. Taken together, our results suggest that curcumin may afford substantial protection against oxidative damage caused by Fe-NTA, and these protective effects may be mediated via its antioxidant properties. These properties of curcumin strongly suggest that it could be used as a cancer chemopreventive agent.

Matched MeSH terms: Carcinogens/administration & dosage*

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