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The Journal of Investigative Dermatology Jun 2022Type 2 inflammation‒related cytokine IL-13 plays a protective role in experimental papilloma induction in mice. To understand the mechanisms by which IL-13 contributes...
Type 2 inflammation‒related cytokine IL-13 plays a protective role in experimental papilloma induction in mice. To understand the mechanisms by which IL-13 contributes to papilloma formation, we utilized Il13rα1-knockout (KO) mice in a widely used 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoyl phorbol-13-acetate two-stage skin carcinogenesis protocol that mimics the development of squamous cell carcinoma. KO mice developed more papillomas and significantly faster than wild-type mice. Papilloma development reduced regulatory T cells in wild-type mice but substantially less in KO mice. In line with this, IL-2 and IL-10 levels decreased in wild-type mice but not in KO mice. Furthermore, systemic IL-5 and TSLP levels were elevated, whereas IL-22 was decreased during papilloma formation in the skin of KO mice. Polymorphonuclear myeloid‒derived suppressor cells were decreased in the KO mice at the early phase of papilloma induction. We show that IL-13Rα1 protects from papilloma development in chemically induced skin carcinogenesis, and our results provide further insights into the protective role of functional IL-4 and IL-13 signaling through type II IL-4 receptor in tumor development.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogenesis; Carcinogens; Interleukin-13; Interleukin-13 Receptor alpha1 Subunit; Mice; Mice, Knockout; Papilloma; Skin Neoplasms; T-Lymphocytes, Regulatory; Tetradecanoylphorbol Acetate
PubMed: 34808240
DOI: 10.1016/j.jid.2021.11.013 -
Scientific Reports May 2023Breast cancer is the second leading cause of cancer death among women. The present study is an effort to reveal the antiproliferative and antioxidant actions of mango...
Breast cancer is the second leading cause of cancer death among women. The present study is an effort to reveal the antiproliferative and antioxidant actions of mango seed kernel extract (KE), peel extract (PE), and their combination (KEPE) on mammary tumors induced by 7,12 dimethylbenz[a]anthracene (DMBA). Seven groups of adult female Sprague-Dawley rats were prepared, including C: (control), DMBA: (rats were administered with DMBA), (DMBA-KE), (DMBA-PE), and (DMBA-KEPE): rats were administered with DMBA and then treated with KE, PE, and (both KE and PE), respectively, (KE) and (PE): rats were administered with KE and PE, separately. The study focused on the assessment of markers of endocrine derangement [serum 17-β estradiol (E2)], apoptosis [caspase-3 and deoxyribonucleic acid fragmentation (DNAF)], and oxidative stress [lipid peroxidation and antioxidants (glutathione, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and superoxide dismutase)]. Histopathological examination and immunohistochemical expression of caspase-3 and estrogen receptor-α (ER-α) in mammary gland tissues (MGTs) were determined, as well as the characterization of mango extracts. The results showed that DMBA administration induced mammary tumors by increasing cell proliferation and evading apoptosis. In addition, DMBA administration caused oxidative stress by the production of reactive oxygen species, which increased lipid peroxidation and decreased cellular antioxidants, allowing cancer to progress. In contrast, treatment with DMBA-KE, DMBA-PE, or DMBA-KEPE diminished mammary tumors induced by DMBA, where they reduced oxidative stress via increased antioxidant parameters including reduced glutathione, superoxide dismutase, total glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Also, different treatments decreased proliferation through the reduction of E2, and ER-α expression levels. However, these treatments increased the apoptosis of unwanted cells as they increased caspase-3 activity and DNAF. All these changes led to the prevention of breast injuries and the reduction of mammary tumors. This demonstrates that the contents of mango extracts, especially phenolics and flavonoids, have an important role in mammary tumor treatment through their potential antioxidant, antiproliferative, proapoptotic, and anti-estrogenic effects. KE and PE administration for 4 weeks had no adverse effects. Conclusion: Each of KE, PE, and KEPE has a therapeutic effect against DMBA-induced mammary tumors via induction of apoptosis and reduction of each of the OS, proliferation, and estrogenic effects. So, they can play an important role in the pharmacological tole.
Topics: Rats; Female; Animals; Antioxidants; Rats, Sprague-Dawley; Mangifera; Caspase 3; 9,10-Dimethyl-1,2-benzanthracene; Mammary Neoplasms, Experimental; Glutathione; Superoxide Dismutase; Carcinogenesis; Oxidoreductases
PubMed: 37169856
DOI: 10.1038/s41598-023-34626-6 -
Journal of Biochemical and Molecular... Jun 2022The objective of this study is to examine the chemopreventive effects of Nerolidol (NER) on hamster buccal pouch carcinogenesis (HBC) induced by...
The objective of this study is to examine the chemopreventive effects of Nerolidol (NER) on hamster buccal pouch carcinogenesis (HBC) induced by 7,12-dimethylbenz(a)anthracene (DMBA) in male golden Syrian hamsters. In this study, oral squamous cell carcinoma was developed in the buccal pouch of an oral painted hamster with 0.5% DMBA in liquid paraffin three times weekly for 12 weeks. To assess DMBA-induced hamster buccal tissue carcinogenesis, biochemical endpoints such as Phase I and II detoxification enzymes, antioxidants, lipid peroxidation (LPO) by-products, and renal function markers, as well as histopathological examinations, were used. Furthermore, the immunohistochemical studies of interleukin-6 were investigated to find the inflammatory link in the HBC carcinogenesis. In our results, DMBA alone exposed hamsters showed 100% tumor growth, altered levels of antioxidants, detoxification agents, LPO, and renal function identifiers as compared to the control hamsters. The outcome in present biochemical, histopathological, and immunohistochemistry studies has been found a reverse in NER-treated hamsters against the tumor. This study concluded that NER modulated the biochemical profiles (antioxidants, detoxification, LPO, and renal function markers) and inhibited tumor development in DMBA induced oral carcinogenesis.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antioxidants; Carcinogenesis; Carcinogens; Carcinoma, Squamous Cell; Cricetinae; Male; Mouth Neoplasms; Sesquiterpenes
PubMed: 35243731
DOI: 10.1002/jbt.23029 -
Naunyn-Schmiedeberg's Archives of... Mar 2023Oxidative stress, a pathological condition, contributes to the pathophysiology of a number of diseases including carcinogenesis. Numerous studies pointed out the...
Oxidative stress, a pathological condition, contributes to the pathophysiology of a number of diseases including carcinogenesis. Numerous studies pointed out the disturbed antioxidants status and accumulation of oxidative stress markers in the carcinogenesis. The present study analyzed the anticancer efficacy of chlorogenic acid-loaded chitosan nanoparticles by utilizing the oxidative stress biomarkers as an endpoint in mice with skin cancer developed by 7,12-dimethylbenz(a)anthracene (DMBA). Oxidative stress markers' (lipid peroxidation by-products and antioxidants) levels or activities were measured using colorimetric assays. While mice exposed with DMBA alone showed a 100% tumor incidence, 0 and 50% tumor formation was seen in mice treated with DMBA + topical application of the nanoparticles and DMBA + orally administered nanoparticles, respectively. Also, the study noticed a 33% and 67% tumor incidence in mice treated with DMBA + topical application of free chlorogenic acid and DMBA + orally administered free chlorogenic acid, respectively. The present study noticed that the topical application of chlorogenic acid-loaded chitosan nanoparticles to DMBA-painted mice completely suppressed the tumor growth and restored the levels or activities of oxidative stress markers as compared to mice that received DMBA + oral administration of chlorogenic acid-loaded chitosan nanoparticles. The study observed that chlorogenic acid-loaded chitosan nanoparticles are more potent than free chlorogenic acid in preventing skin cancer in mice caused by DMBA. Thus, the present investigation explores the tumor-inhibiting efficacy of chlorogenic acid-loaded chitosan nanoparticles in experimental skin cancer, and the tumor preventive efficiency could be attributed to their antilipid peroxidative and antioxidant effects.
Topics: Animals; Mice; Antioxidants; 9,10-Dimethyl-1,2-benzanthracene; Chlorogenic Acid; Chitosan; Carcinoma, Squamous Cell; Carcinogenesis; Skin Neoplasms; Nanoparticles
PubMed: 36418466
DOI: 10.1007/s00210-022-02330-3 -
Environmental Toxicology Mar 2021Humans are daily exposed to 7,12-dimethylbenz(a)anthracene (DMBA), a well known polycyclic aromatic hydrocarbons (PAH). This study investigated the role of dietary...
Humans are daily exposed to 7,12-dimethylbenz(a)anthracene (DMBA), a well known polycyclic aromatic hydrocarbons (PAH). This study investigated the role of dietary intake of Vitamin K (VK), a polyphenolic compound, with potential antioxidative properties, against DMBA-induced hepatotoxicity. Sixty experimental animals (120-150 g) were divided into six groups (A-F): Control, DMBA (80 mg/kg bw) only, VK (0.00 g/10 kg) diet only, VK (7.5 g/10 kg) diet only, DMBA + VK (0.0 g/10 kg) diet and DMBA + VK (7.5 g/10 kg) diet. Single oral administration of DMBA (80 mg/kg body weight) to Wistar rats resulted in hepatic damage after 16 weeks. DMBA significantly (P < .05) decreased the activities of catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione peroxidase (GPx). Levels of reduced glutathione (GSH) and Vitamin C were significantly decreased with increase in malondialdehyde (MDA) and nitric oxide (NO) levels in serum and liver. Aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities were significantly (P < .05) elevated in the serum but reduced in the liver of DMBA-administered group. Ingestion of 7.5 g/10 kg VK diet prevented the up regulations in inflammatory biomarkers (granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin 17A (IL-17A)) which elicited liver damaged in the DMBA-treated group. DMBA induced hepatic alterations in DMBA-treated group but was restored to near normal in VK (7.5 g/10 kg) diet group. These findings suggest the protective potential of increased dietary intake of vitamin K against DMBA-induced hepatic dysfunction.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anthracenes; Antioxidants; Ascorbic Acid; Catalase; Chemical and Drug Induced Liver Injury; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Liver; Male; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase; Vitamin K
PubMed: 33063951
DOI: 10.1002/tox.23042 -
Current Medical Science Dec 2021Autophagy is a programmed cell death procedure, which has essential functions in tumorigenesis. However, its temporal expression and function under different status are...
OBJECTIVE
Autophagy is a programmed cell death procedure, which has essential functions in tumorigenesis. However, its temporal expression and function under different status are yet to be determined. This study aims to investigate the temporal expression of autophagy and its possible function in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal-pouch cancer model (HBPCM).
METHODS
A total of 50 hamster buccal-pouch tumorigenesis models were established by painting DMBA for 4, 8, 10 and 13 weeks. The expression and subcellular localization of LC3, Beclin 1 and Bcl-2 in buccal lesions were evaluated by immunohistochemical staining and Western blotting. DNA damage was observed by immunohistochemical staining of 8-oHdG. The relationship between Beclin 1 and Bcl-2 was analyzed by immunofluorescence colocalization.
RESULTS
The expression levels of LC3 and Beclin 1 associated with autophagy in the experimental buccal pouch of HBPCM were significantly upregulated after 4 weeks (P<0.05), but gradually downregulated after 13 weeks of HBPCM induction. By contrast, the expression level of Bcl-2 was significantly upregulated after 13 weeks. The co-localized regions of Bcl-2 and Beclin 1 peaked after 4 weeks and then decreased gradually. The DNA damage in epithelial cells increased slightly after 4 weeks, and then rapidly decreased over the next 2 months.
CONCLUSION
Autophagy is motivated by a tumor suppressor that diminishes carcinogen-induced DNA damage. However, autophagy is gradually suppressed, which may be attributed to the interaction between Bcl-2 and Beclin 1. This result indicates that the promotion of autophagy may suppress malignant transformation and provide new insights on future potential treatments of HBPCM.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; Autophagy; Beclin-1; Carcinogenesis; Carcinogens; Carcinoma, Squamous Cell; Cheek; Cricetinae; Epithelial Cells; Immunohistochemistry; Mouth Neoplasms; Proto-Oncogene Proteins c-bcl-2; Time Factors
PubMed: 34950986
DOI: 10.1007/s11596-021-2472-5 -
Journal of Ethnopharmacology Dec 2020Skin cancer is the most common form of cancer responsible for considerable morbidity and mortality. Tieghemella africana and Ficus vogeliana are used in traditional...
ETHNOPHARMACOLOGICAL RELEVANCE
Skin cancer is the most common form of cancer responsible for considerable morbidity and mortality. Tieghemella africana and Ficus vogeliana are used in traditional medicine to treat cancers.
AIM OF THE STUDY
Therefore, the aim of this study was to investigate the antioxidant, antiangiogenic and anti-tumor activities of these plant extracts.
MATERIALS AND METHODS
To achieve it, phytochemical screening, antioxidant activity and antiangiogenic activity were assessed. Thereafter, the anti-tumor activity was determined using skin tumorigenesis induced by 7,12-dimethylbenz[a]anthracene.
RESULTS
The phytochemical result analysis showed that both plant extracts were rich in polyphenols, alkaloids and terpene compounds and possessed good antioxidant activity based on DPPH radical scavenging (IC = 9.70 μg/mL and 4.60 μg/mL and AAI values of 5.20 and 10.88) and strong total antioxidant capacity (115.44 VtCE (mg)/g of dry plant extract and 87.37 VtCE (mg)/g of dry plant extract, respectively). Additionally, both plant extracts possessed antiangiogenic activities (IC = 53.43 μg/mL and 92.68 μg/mL, respectively), which correlated with significant antitumor activities when using 35 mg/kg (65.02% and 77.54%) and 70 mg/kg of extracts (81.07% and 88.18%).
CONCLUSIONS
In summary, this study illustrates the promising usage of Tieghemella africana and Ficus vogeliana plant extracts in treating skin cancer. However, further characterization of the extracts must be performed to isolate the most active anticancer compound.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Chick Embryo; Ficus; Male; Plant Extracts; Rats; Rats, Wistar; Sapotaceae; Skin Neoplasms; Treatment Outcome; Water
PubMed: 32800931
DOI: 10.1016/j.jep.2020.113244 -
International Journal of Molecular... Jan 2022Endocrine-disrupting chemicals (EDCs)-including butyl benzyl phthalate (BBP), perfluorooctanoic acid (PFOA), and zeranol (α-ZAL, referred to as ZAL hereafter)-can...
Endocrine-disrupting chemicals (EDCs)-including butyl benzyl phthalate (BBP), perfluorooctanoic acid (PFOA), and zeranol (α-ZAL, referred to as ZAL hereafter)-can interfere with the endocrine system and produce adverse effects. It remains unclear whether pubertal exposure to low doses of BBP, PFOA, and ZAL has an impact on breast development and tumorigenesis. We exposed female Sprague Dawley rats to BBP, PFOA, or ZAL through gavage for 21 days, starting on day 21, and analyzed their endocrine organs, serum hormones, mammary glands, and transcriptomic profiles of the mammary glands at days 50 and 100. We also conducted a tumorigenesis study for rats treated with PFOA and ZAL using a 7,12-dimethylbenz[a]anthracene (DMBA) model. Our results demonstrated that pubertal exposure to BBP, PFOA, and ZAL affected endocrine organs and serum hormones, and induced phenotypic and transcriptomic changes. The exposure to PFOA + ZAL induced the most phenotypic and transcriptomic changes in the mammary gland. PFOA + ZAL downregulated the expression of genes related to development at day 50, whereas it upregulated genes associated with tumorigenesis at day 100. PFOA + ZAL exposure also decreased rat mammary tumor latency, reduced the overall survival of rats after DMBA challenge, and affected the histopathology of mammary tumors. Therefore, our study suggests that exposure to low doses of EDCs during the pubertal period could induce changes in the endocrine system and mammary gland development in rats. The inhibition of mammary gland development by PFOA + ZAL might increase the risk of developing mammary tumors through activation of signaling pathways associated with tumorigenesis.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Caprylates; Carcinogenesis; Cell Transformation, Neoplastic; Endocrine Disruptors; Female; Fluorocarbons; Hormones; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Phthalic Acids; Rats; Rats, Sprague-Dawley; Zeranol
PubMed: 35163327
DOI: 10.3390/ijms23031398 -
Experimental and Molecular Pathology Dec 2019Advances in our understanding of the metabolism and molecular functions of arginine and their alterations in cancer have led to resurgence in the interest of targeting...
Advances in our understanding of the metabolism and molecular functions of arginine and their alterations in cancer have led to resurgence in the interest of targeting arginine catabolism as an anticancer strategy. Therefore, arginase inhibitors have been proposed as a way to treat cancer. In this study, the anti-tumor potential of the arginase inhibition by N-hydroxy-nor-L-arginine (nor-NOHA) (3 mg/kg/day, i.p.), administered for 5 weeks (parallel tumors development, every 3th day) against 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis in rats has been investigated. Treatment by nor-NOHA has obvious inhibition effects on development of carcinogenesis in rats was shown. That was seen in downregulation of rats' tumors size and number, mortality rate, in stopped alteration of tissue histopathology, in decrease of polyamines, NO and MDA (malondialdeide) concentrations (in blood). Results have shown arginase and NO-synthase can cooperate to restrain quantities of polyamines and NO for cancer progression. The results obtained can serve as a base to use this model for determination of productive, noncytotoxic antitumor and immune modulating concentration of anticancer agents. Perspectives of targeting arginase and NOS in cancer management can ground application in clinical medicine.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents; Arginase; Arginine; Breast Neoplasms; Female; Mortality; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress; Polyamines; Rats, Wistar
PubMed: 31629728
DOI: 10.1016/j.yexmp.2019.104316 -
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