-
Asian Pacific Journal of Cancer... Aug 2022Oral squamous cell carcinoma (OSCC) is the most common form of oral cancer, showing poor prognosis and high mortality. Meanwhile, cancer metabolism is an essential...
BACKGROUND AND AIM OF THE STUDY
Oral squamous cell carcinoma (OSCC) is the most common form of oral cancer, showing poor prognosis and high mortality. Meanwhile, cancer metabolism is an essential contributor to its progression and response to treatment. This research aims to investigating the effect of a glucose-rich and glucose-free diet on the progress of oral squamous cell carcinoma induced in hamsters.
MATERIALS AND METHODS
forty Syrian Hamsters were incubated in two groups. The first one consisted of twenty hamsters, in which the carcinogenic material (DMBA) was applied in the buccal pouch of the hamster three days per week with a glucose-rich diet). The second one was composed of twenty hamsters, in which the carcinogenic material (DMBA) was applied in the buccal pouch three days per week with a glucose-free diet). Hamsters in both groups were sacrificed in groups of five hamsters at a time and at intervals (two weeks, six weeks, ten weeks, and Fourteen weeks). A histological study was performed after conventional staining with hematoxylin and eosin was done.
RESULTS
After two weeks of the experiment hyperplasia, mild dysplasia, and moderate dysplasia were recorded in hamster buccal pockets with a glucose-rich diet, and after six weeks moderate dysplasia, severe dysplasia, and carcinomas in situ were recorded, after ten weeks severe dysplasia, carcinomas in situ, and OSCC, after fourteen weeks OSCC were recorded. While with a glucose-free diet Hyperkeratosis, hyperplasia, and mild dysplasia were observed after a two-week the experiment, after six weeks, mild dysplasia, moderate dysplasia, and severe dysplasia were recorded, after ten weeks, moderate dysplasia, severe dysplasia, and carcinoma in situ, after fourteen weeks Severe dysplasia, carcinoma in situ, and OSCC were reported.
CONCLUSION
our results showed that a glucose-free diet slightly prevents oral squamous cell carcinoma, It may be a supportive treatment in addition to conventional cancer treatment.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogenesis; Carcinogens; Carcinoma in Situ; Carcinoma, Squamous Cell; Cricetinae; Glucose; Head and Neck Neoplasms; Humans; Hyperplasia; Mesocricetus; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 36037144
DOI: 10.31557/APJCP.2022.23.8.2857 -
The Journal of Toxicological Sciences 2022Testicular Leydig cells produce testosterone through the participation of steroidogenic proteins. The CYP1B1 enzyme has been shown to catalyze...
Testicular Leydig cells produce testosterone through the participation of steroidogenic proteins. The CYP1B1 enzyme has been shown to catalyze 7,12-dimethylbenzanthracene (DMBA), a representative polycyclic aromatic hydrocarbon. We hypothesized that exposure to DMBA causes Leydig cell cytotoxicity through activation of CYP1B1. Leydig cells were exposed to various concentrations of DMBA for the induction of CYP1B1 expression and activity. The status of CYP1B1 function was monitored by evaluation of cytotoxicity-mediated cell death. Our data show that exposure to DMBA causes cytotoxicity in Leydig cells by CYP1B1 activation. DMBA evoked a significant increase in the generation of reactive oxygen species (ROS) by which the depolarization of mitochondrial membrane potential (MMP) is initiated and caspase-3 activation is augmented. The knockdown of CYP1B1 expression resulted in the suppression of DMBA-induced apoptosis via reduced p53 activation and caspase-3 activation, suggesting that a final metabolite of DMBA (i.e., DMBA-DE) bioactivated by CYP1B1 induces p53 activation by binding to DNA and subsequently causing apoptosis via caspase-3 activation. This finding provides evidence for constitutive expression of CYP1B1 in Leydig cells, which is a trait that only requires an initiating signal for its activity. Further research on CYP1B1 activation-provoked steroid metabolism in Leydig cells may provide decisive clues for elucidating its innate function.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Apoptosis; Caspase 3; Cytochrome P-450 CYP1B1; Humans; Leydig Cells; Male; Tumor Suppressor Protein p53
PubMed: 35908932
DOI: 10.2131/jts.47.317 -
EMBO Reports Jun 2022Interleukin-38 (IL-38) is strongly associated with chronic inflammatory diseases; however, its role in tumorigenesis is poorly understood. We demonstrated that...
Interleukin-38 (IL-38) is strongly associated with chronic inflammatory diseases; however, its role in tumorigenesis is poorly understood. We demonstrated that expression of IL-38, which exhibits high expression in the skin, is downregulated in human cutaneous squamous cell carcinoma and 7,12-dimethylbenzanthracene/12-O-tetradecanoyl phorbol-13-acetate-induced mouse skin tumorigenesis. IL-38 keratinocyte-specific knockout mice displayed suppressed skin tumor formation and malignant progression. Keratinocyte-specific deletion of IL-38 was associated with reduced expression of inflammatory cytokines, leading to reduced myeloid cell infiltration into the local tumor microenvironment. IL-38 is dispensable for epidermal mutagenesis, but IL-38 keratinocyte-specific deletion reduces proliferative gene expression along with epidermal cell proliferation and hyperplasia. Mechanistically, we first demonstrated that IL-38 activates the c-Jun N-terminal kinase (JNK)/activator protein 1 signal transduction pathway to promote the expression of cancer-related inflammatory cytokines and proliferation and migration of tumor cells in an IL-1 receptor-related protein 2 (IL-1Rrp2)-dependent manner. Our findings highlight the role of IL-38 in the regulation of epidermal cell hyperplasia and pro-tumorigenic microenvironment through IL-1Rrp2/JNK and suggest IL-38/IL-1Rrp2 as a preventive and potential therapeutic target in skin cancer.
Topics: Animals; Carcinogenesis; Carcinoma, Squamous Cell; Cytokines; Hyperplasia; Interleukin-1; Interleukins; Mice; Receptors, Interleukin-1; Skin; Skin Neoplasms; Tumor Microenvironment
PubMed: 35578812
DOI: 10.15252/embr.202153791 -
Cells Apr 2022Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea () extract, polyphenol extract (a mixture of blackberry (),...
Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea () extract, polyphenol extract (a mixture of blackberry (), blackcurrants (), and added resveratrol phytoalexin), Chinese bayberry () extract, and a coffee () extract on 7,12-dimethylbenz[a]anthracene (DMBA) carcinogen-increased miR-134, miR-132, miR-124-1, miR-9-3, and gene expressions in the liver, spleen, and kidneys of CBA/Ca mice. The elevation was quenched significantly in the organs, except for miR-132 in the liver of the Chinese bayberry extract-consuming group, and miR-132 in the kidneys of the polyphenol-fed group. In the coffee extract-consuming group, only miR-9-3 and mTOR decreased significantly in the liver; also, miR-134 decreased significantly in the spleen, and, additionally, miR-124-1 decreased significantly in the kidney. Our results are supported by literature data, particularly the DMBA generated ROS-induced inflammatory and proliferative signal transducers, such as TNF, IL1, IL6, and NF-κB; as well as oncogenes, namely and . The examined chemopreventive agents, besides the obvious antioxidant and anti-inflammatory effects, mainly blocked the mentioned DMBA-activated factors and the mitogen-activated protein kinase (MAPK) as well, and, at the same time, induced as well as tumor suppressor genes.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Biomarkers; Coffee; Gene Expression; Mice; Mice, Inbred CBA; MicroRNAs; Polyphenols; TOR Serine-Threonine Kinases
PubMed: 35455979
DOI: 10.3390/cells11081300 -
Cancer Treatment and Research... 2022The current study was directed to investigate the effectiveness of docosahexaenoic acid (DHA) as a chemopreventive agent on experimentally induced hamster buccal pouch...
PURPOSE
The current study was directed to investigate the effectiveness of docosahexaenoic acid (DHA) as a chemopreventive agent on experimentally induced hamster buccal pouch (HBP) carcinogenesis.
MATERIAL AND METHODS
In this study we used 40 Syrian male hamsters, five weeks old, were divided into 4 groups (GI, GII, GIII, and GIV) of 10 animals in each as follows, GI: Topical application of liquid paraffin alone (thrice a week for 14 weeks), GII: Topical application of 7, 12 dimethyl benz[a]anthracene (DMBA) alone (0.5% in liquid paraffin, thrice a week for 14 weeks), GIII: Topical application of DMBA (0.5% in liquid paraffin, thrice a week for 14 weeks) + Oral administration of DHA (125 mg/kg b.w. in 1 ml distilled water by oral gavage, thrice a week for 14 weeks on alternative days of DMBA application), GIV: Oral administration of DHA alone (125 mg/kg b.w. in 1 ml distilled water by oral gavage, thrice a week for 14 weeks).
RESULTS
Gross observations and histopathological findings revealed that, in GI: normal stratified squamous epithelium, in GII: well and moderately differentiated squamous cell carcinoma (SCC), in GIII: variable results ranges from hyperkeratosis, hyperkeratosis and focal hyperplasia, mild dysplasia, and well differentiated SCC with superficial invasion of tumor cells not extended to deeper areas, while in GIV: normal similar to GI. Immunohistochemical results indicated that oral DHA treatment to DMBA treated hamsters restored the normal expression of bcl-2.
CONCLUSION
Our results indicated that DHA has the potential to be a dietary chemopreventive agent due to its capacity to improve carcinogen detoxification and to block/suppress the initiation and promotion stages of experimentally produced HBP carcinogenesis.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogenesis; Carcinoma, Squamous Cell; Cricetinae; Docosahexaenoic Acids; Humans; Lipid Peroxidation; Male; Mesocricetus; Mineral Oil; Mouth Mucosa; Mouth Neoplasms; Water
PubMed: 35443225
DOI: 10.1016/j.ctarc.2022.100558 -
Asian Pacific Journal of Cancer... Mar 2022Breast cancer prevention still needs to be improved. Calorie restriction is thought to prevent breast cancer through the induction of autophagy. Maranta arundinacea L....
BACKGROUND
Breast cancer prevention still needs to be improved. Calorie restriction is thought to prevent breast cancer through the induction of autophagy. Maranta arundinacea L. (MA) has the potential for calorie restriction because it contains high fiber. This research aimed to observe the effect of dietary MA against dimethylbenz(a)anthracene (DMBA)-induced mammary cancer in Sprague Dawley rats related to autophagy.
METHODS
Twenty-five Sprague Dawley rats were randomly divided into five groups: 1) control group without DMBA-induced with a standard diet, 2) 20 mg/kg BW of DMBA two times a week for five weeks with a standard diet, 3) DMBA and diet modification with 30% of MA, 4) DMBA and diet modification with 45% of MA, and 5) DMBA and diet modification with 60% of MA. Examination of the nodule was conducted once every week for 22 weeks. Breast tissue/tumor examination underwent histology examination with hematoxylin-eosin. Examinations of immunohistochemical staining against Beclin1, LC3B, and SQSTM1 were conducted to reveal autophagy. The difference of autophagy protein expression was analyzed using One way ANOVA with 95% confidence level and significance set as p<0.05.
RESULTS
Cancer was detected in four rats of DMBA standard diet, two rats of 30% MA, one rat of 45% MA. No cancer was detected in the rats of control and rats with 60% of MA group. The Beclin1 expressions showed that the 60% of MA group had the highest score (2.5±0.52) followed by the 45% of MA group (1.87±0.49), control group (1.77±0.11), 30% of MA group (1.28±0.75), and DMBA with standard diet had the lowest score (1.28±0.91). The difference of Beclin1 expressions was statistically significant (p-value=0.03). However, the difference of the LC3B expressions (p-value=0.11) and SQSTM1 expressions (p-value=0.225) were not statistically significant.
CONCLUSION
Dietary modifications with MA potentially prevent breast cancer and induce initiation of autophagy.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Autophagy; Breast Neoplasms; Diet; Female; Humans; Mammary Neoplasms, Experimental; Marantaceae; Rats; Rats, Sprague-Dawley
PubMed: 35345372
DOI: 10.31557/APJCP.2022.23.3.985 -
Cells Mar 2022Specific gene and miRNA expression patterns are potential early biomarkers of harmful environmental carcinogen exposures. The aim of our research was to develop an assay...
Specific gene and miRNA expression patterns are potential early biomarkers of harmful environmental carcinogen exposures. The aim of our research was to develop an assay panel by using several miRNAs for the rapid screening of potential carcinogens. The expression changes of miR-124-1, miR-212, miR-132, miR-134, and miR-155 were examined in the spleen, liver, and kidneys of CBA/Ca mice, following the 20 mg/bwkg intraperitoneal 7,12-dimethylbenz(a)anthracene (DMBA) treatment. After 24 h RNA was isolated, the miRNA expressions were analyzed by a real-time polymerase chain reaction and compared to a non-treated control. DMBA induced significant changes in the expression of miR-134, miR-132, and miR-124-1 in all examined organs in female mice. Thus, miR-134, miR-132, and miR-124-1 were found to be suitable biomarkers for the rapid screening of potential chemical carcinogens and presumably to monitor the protective effects of chemopreventive agents.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anthracenes; Carcinogens; Female; Mice; Mice, Inbred CBA; MicroRNAs
PubMed: 35326471
DOI: 10.3390/cells11061020 -
Scientific Reports Mar 2022Imbalanced glucose tolerance and insulin resistance remain important as high cancer risk factors. Metformin administration to diabetic patients may be associated with a...
Imbalanced glucose tolerance and insulin resistance remain important as high cancer risk factors. Metformin administration to diabetic patients may be associated with a reduced risk of malignancy. The combined effects of the hormone melatonin and metformin in oncology practice have shown positive results. The relevance of our study is to find out the role of specific biomarkers of lysosome destruction and oxidative stress data in carcinogenesis models. The present study was designed to investigate the comparative synergic effect of peroral antidiabetic metformin (MF) and pineal hormone melatonin (MEL) administered alone and in combination in two different rat's models of mammary tumour proliferation in vivo (N-methyl-N-nitrosourea, NMU or 7,12-dimethylbenz[a]anthracene, DMBA). We have studied the processes of lysosomal destruction (alanyl aminopeptidase AAP, leucyl aminopeptidase LAP, acid phosphatase AcP, β-N-acetylglucosaminidase NAG, β-galactosidase β-GD and β-glucuronidase β-GR) caused by evaluated oxidative stress in three types of tissues (liver, heart, and spleen) in female Sprague-Dawley rats fed a high-fat diet (10% of total fat: 2.5% from lard and 7.5% from palm olein). Our results revealed an increase in the activity of the studied lysosomal enzymes and their expression in a tissue-specific manner depending on the type of chemical agent (NMU or DMBA). MANOVA tests in our study confirmed the influence of the three main factors, type of tissue, chemical impact, and chemopreventive agents, and the combinations of these factors on the lysosomal activity induced during the process of cancerogenesis. The development and induction of the carcinogenesis process in the different rat models with the high-fat diet impact were also accompanied by initiation of free-radical oxidation processes, which we studied at the initial (estimated by the level of diene conjugates) and final (TBARS products) stages of this process. The combined effects of MEL and MF for the two models of carcinogenesis at high-fat diet impact for AAP, LAP, and AcP showed a significant synergistic effect when they impact together when compared with the effects of one substance alone (either MEL or MF) in the breast cancer model experiments. Synergistic effects of limiting destructive processes of lysosomal functioning β-GD enzyme activity we obtained in experiments with MEL and MF chemoprevention for both models of carcinogenesis for three tissues. The statistical SS test allowed us to draw the following conclusions on the role of each lysosomal parameter analyzed as an integral model: NAG > AcP > β-GD > β-GR > AAP > LAP.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Autophagy; Carcinogenesis; Diet, High-Fat; Female; Humans; Lysosomes; Mammary Neoplasms, Experimental; Melatonin; Metformin; Oxidative Stress; Rats; Rats, Sprague-Dawley
PubMed: 35322049
DOI: 10.1038/s41598-022-08778-w -
The Journal of Investigative Dermatology Sep 2022P2RY6 is highly expressed in skin keratinocytes, but its function in skin diseases is unclear. We use a two-step chemical induction method to induce mouse skin tumor...
P2RY6 is highly expressed in skin keratinocytes, but its function in skin diseases is unclear. We use a two-step chemical induction method to induce mouse skin tumor formation. Multiple in vitro and in vivo assays were used to explore the role of P2RY6 in skin tumors. We report that P2ry6-deficient mice exhibit marked resistance to 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin papilloma formation compared with wild-type mice. Consistent with these findings, epidermal hyperplasia in response to TPA was suppressed in the P2ry6-knockout or MRS2578 (P2RY6 antagonist)-treated mice. The dramatic decrease in hyperplasia and tumorigenesis due to P2ry6 disruption was associated with the suppression of TPA-induced keratinocyte proliferation and inflammatory reactions. Notably, P2ry6 deletion prevented the TPA-induced increase in YAP nuclear accumulation and its downstream gene expression in an MST/LATS1-dependent manner. On TPA stimulation, enhanced activation of MAPK/extracellular signal‒regulated kinase kinase 1 and β-catenin were also impaired in P2ry6-knockout primary keratinocytes, tumor tissues, or MRS2578-treated HaCaT cells. Moreover, mutual promotion of the YAP and β-catenin signaling pathways was observed in normal skin cells treated with TPA, whereas P2ry6 deletion could inhibit their crosstalk by regulating MAPK/extracellular signal‒regulated kinase kinase 1. Thus, P2RY6 is a critical positive regulator of skin tumorigenesis through the modulation of the Hippo/YAP and Wnt/β-catenin signaling pathways.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogenesis; Hyperplasia; Keratinocytes; Mice; Receptors, Purinergic P2; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Wnt Signaling Pathway; YAP-Signaling Proteins; beta Catenin
PubMed: 35304248
DOI: 10.1016/j.jid.2022.02.017 -
Pharmaceutics Feb 2022Oxidative stress and inflammation act on skin squamous cell carcinoma (SSCC) development and progression. Curative therapy for SSCC patients is mainly based on surgical...
Oxidative stress and inflammation act on skin squamous cell carcinoma (SSCC) development and progression. Curative therapy for SSCC patients is mainly based on surgical resection, which can cause various sequelae. Silver ions have in vitro activities over tumor cells, while nimesulide has antioxidant and anti-inflammatory activities. This study aimed to evaluate the effects of a silver(I) complex with nimesulide (AgNMS) incorporated in a sustained release device based on bacterial cellulose membrane, named AgNMS@BCM, on topic SSCC treatment. The antiproliferative effect of AgNMS complex was evaluated in the SCC4, SCC15 and FaDu SCC lines. AgNMS complex activity on exposure of phosphatidylserine (PS) residues and multicaspase activation were evaluated on FaDu cells by flow cytometry. The AgNMS@BCM effects were evaluated in a SSCC model induced by 7,12-dimethylbenzanthracene/12--tetradecanoyl-phorbol-13-acetate (DMBA/TPA) in mice. Toxicity and tumor size were evaluated throughout the study. AgNMS complex showed antiproliferative activity in SCC15 and FaDu lines in low to moderate concentrations (67.3 µM and 107.3 µM, respectively), and induced multicaspase activation on FaDu cells. The AgNMS@BCM did not induce toxicity and reduced tumor size up to 100%. Thus, the application of AgNMS@BCM was effective and safe in SSCC treatment in mice, and can be seen as a potential and safe agent for topic treatment of SSCC in humans.
PubMed: 35214194
DOI: 10.3390/pharmaceutics14020462