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Oncogene May 2021Cutaneous squamous cell carcinoma (cSCC) ranks second in the frequency of all skin cancers. The balance between keratinocyte proliferation and differentiation is...
Cutaneous squamous cell carcinoma (cSCC) ranks second in the frequency of all skin cancers. The balance between keratinocyte proliferation and differentiation is disrupted in the pathological development of cSCC. DLX3 is a homeobox transcription factor which plays pivotal roles in embryonic development and epidermal homeostasis. To investigate the impact of DLX3 expression on cSCC prognosis, we carried out clinicopathologic analysis of DLX3 expression which showed statistical correlation between tumors of higher pathologic grade and levels of DLX3 protein expression. Further, Kaplan-Meier survival curve analysis demonstrated that low DLX3 expression correlated with poor patient survival. To model the function of Dlx3 in skin tumorigenesis, a two-stage dimethylbenzanthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA) study was performed on mice genetically depleted of Dlx3 in skin epithelium (Dlx3cKO). Dlx3cKO mice developed significantly more tumors, with more rapid tumorigenesis compared to control mice. In Dlx3cKO mice treated only with DMBA, tumors developed after ~16 weeks suggesting that loss of Dlx3 has a tumor promoting effect. Whole transcriptome analysis of tumor and skin tissue from our mouse model revealed spontaneous activation of the EGFR-ERBB2 pathway in the absence of Dlx3. Together, our findings from human and mouse model system support a tumor suppressive function for DLX3 in skin and underscore the efficacy of therapeutic approaches that target EGFR-ERBB2 pathway.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Aged; Animals; Carcinogens; Carcinoma, Squamous Cell; Disease Models, Animal; ErbB Receptors; Female; Homeodomain Proteins; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neoplasm Grading; Receptor, ErbB-2; Signal Transduction; Skin Neoplasms; Survival Rate; Tetradecanoylphorbol Acetate; Transcription Factors
PubMed: 33947961
DOI: 10.1038/s41388-021-01802-9 -
Scientific Reports Oct 2023Dietary components have recently received rapidly expanding attention for their potential to halt or reverse the development of many oxidative stress-mediated diseases...
Dietary components have recently received rapidly expanding attention for their potential to halt or reverse the development of many oxidative stress-mediated diseases after exposure to environmental toxicants. 7, 12 dimethylbenz(a)anthracene (DMBA) is one of the most common environmental pollutants. The present study aimed to evaluate the chemo-preventive effects of broccoli as a nutritional component against DMBA intoxication in rats. A daily dose of aqueous (1 ml/rat) and methanolic (150 mg/kg) broccoli extracts, respectively, was given to 50-day-old female rats for 26 successive weeks after carcinogen intoxication with a single dose of 20 mg/ml of DMBA. DMBA intoxication resulted in a redox imbalance (a decreased GSH level and an increased MDA level) and increased DNA fragmentation in the liver, kidney, and brain. Besides, it affected the level of expression of the bcl2 gene in the liver, kidney, and brain tissue but didn't affect cfos gene expression accompanied by histopathological changes. The aqueous and methanolic broccoli extract supplements ameliorated the adverse effects by increasing the level of GSH, decreasing the MDA level, and reducing DNA fragmentation. Besides, broccoli extracts decreased the expression of bcl2 in the liver and brain and up-regulated bcl2 expression in the kidney, accompanied by lowering NF-κβ 65 expression in the liver and brain and γ-catenin expression in the liver and kidney. In conclusion, broccoli as a dietary component had a strong chemoprotective effect against oxidative stress, DNA damage, and genotoxicity induced by DMBA intoxication in rats.
Topics: Rats; Female; Animals; 9,10-Dimethyl-1,2-benzanthracene; Brassica; Anticarcinogenic Agents; Proto-Oncogene Proteins c-bcl-2; Dietary Supplements; Anthracenes
PubMed: 37821474
DOI: 10.1038/s41598-023-43629-2 -
Experimental Animals Aug 2019Serous borderline ovarian tumors (SBOTs) behave between benign cystadenomas and carcinomas, and the effective detection and clinical management of SBOTs remain clinical...
Serous borderline ovarian tumors (SBOTs) behave between benign cystadenomas and carcinomas, and the effective detection and clinical management of SBOTs remain clinical challenges. Because it is difficult to isolate and enrich borderline tumor cells, a borderline animal model is in need. 7,12-dimethylbenz[a]anthracene (DMBA) is capable of inducing the initiation, promotion, and progression of serous ovarian tumors. This study aims to investigate the proper dosage and induction time of DMBA for rat models of SBOTs, and explore their morphological features demonstrated by magnetic resonance (MR) imaging and molecular genetic characteristics. Rats were randomly divided into six groups (1 mg/70 D, 2 mg/70 D, 3 mg/70 D, 2 mg/50 D, 2 mg/90 D, and 2 mg/110 D). The 3 mg/70 D group induced the most SBOTs (50.0%, 12/24). The micropapillary projections were shown on MR imaging, which was the characteristic of SBOTs. The Cyclin D1 characterizing an early pathogenetic event strongly expressed in induced serous benign tumors (SBTs). The immunoreactivity staining scores of P53 expression significantly increased from SBTs, SBOTs to serous ovarian carcinomas (SCAs), which elucidate that P53 might be a promising biomarker to grade serous ovarian tumors. Based on morphological and molecular genetic similarities, this rodent SBOT model was suitable for investigating the pathogenesis of serous ovarian tumors and developing an early detection strategy.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Ovarian Neoplasms; Random Allocation; Rats; Rats, Sprague-Dawley; Time Factors
PubMed: 30760660
DOI: 10.1538/expanim.18-0103 -
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 -
Nutrition and Cancer 2021Virgin coconut oil (VCO) and turmeric are traditionally being used in Indian cuisine systems; VCO is a natural combination of medium-chain triglyceride and polyphenols...
Virgin coconut oil (VCO) and turmeric are traditionally being used in Indian cuisine systems; VCO is a natural combination of medium-chain triglyceride and polyphenols with established pharmacological potential. Curcumin isolated from turmeric is renowned for its anticancer properties, however, with limited clinical success due to poor bioavailability. Considering the lipophilic nature of VCO, curcumin added to VCO is expected to have synergistic/additive actions. In this study, the chemopreventive potential of curcumin enriched VCO (VCr) (4 and 8 mL/Kg orally) was analyzed in 7,12-dimethyl benz[a]anthracene (DMBA;470 nmoles/200 µL/week for two weeks topical)/croton oil (3% v/v in 200 µL acetone twice a week for 6 weeks topical) induced skin papilloma. In DMBA control animals, an average incidence of 13 papilloma/mice (latency period of 11.6 ± 1.5 weeks) was recorded. Pretreatment with VCrH (8 mL/kg) had a 60% inhibition of tumor index, and an increased latency period (12.5 ± 0.9 weeks). Additionally, DMBA/croton oil-induced reduction in glutathione levels and concomitant increase in thiobarbituric acid reactive substance (TBARS) in the skin microenvironment were restored by VCr. The study thus suggests that the VCr promotes antioxidant status and imparts an improved anticarcinogenic potential. However, further studies are necessary to ascertain the improvement in bioavailability of curcumin .
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anthracenes; Coconut Oil; Curcumin; Mice; Papilloma; Plant Extracts; Skin Neoplasms; Tumor Microenvironment
PubMed: 32530305
DOI: 10.1080/01635581.2020.1778745 -
Expert Opinion on Therapeutic Targets Feb 2020: The purpose of the present study was to examine the chemopreventive effect of stampidine, an aryl phosphate derivative of stavudine, in side by side comparison with... (Comparative Study)
Comparative Study
: The purpose of the present study was to examine the chemopreventive effect of stampidine, an aryl phosphate derivative of stavudine, in side by side comparison with the standard anti-breast cancer drug paclitaxel in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)-induced murine breast cancer model.: Groups of 20 female mice were challenged with the DMBA. DMBA-challenged mice were assigned to various chemoprevention treatments, including stampidine, paclitaxel, and stampidine plus paclitaxel according to the same treatment schedules for 25 weeks.: Stampidine resulted in substantially reduced numbers of tumors, tumor weight as well as tumor size in DMBA-treated mice. Stampidine was as effective as paclitaxel in the model and their combination exhibited greater chemopreventive activity, as measured by reduced tumor incidence and improved tumor-free survival as well as overall survival of DMBA-treated mice. The length of time for the initial tumor to appear in DMBA-challenged mice treated with stampidine was longer than that of mice treated DMBA-challenged control mice. Tumors from mice treated with stampidine or stampidine plus paclitaxel displayed unique changes of a signature protein cassette comprised BRCA1, p21, Bax, and Bcl-2.: Stampidine has potent chemopreventive activity and is as effective as the standard chemotherapy drug paclitaxel in the chemical carcinogenesis.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Breast Neoplasms; Dideoxynucleotides; Disease Models, Animal; Disease-Free Survival; Female; Mice; Mice, Inbred BALB C; Paclitaxel; Stavudine; Survival Rate; Thymidine Monophosphate; Time Factors
PubMed: 32005098
DOI: 10.1080/14728222.2020.1724961 -
Communications Biology Oct 2023Mammary cancer incidence varies greatly across species and underlying mechanisms remain elusive. We previously showed that mammosphere-derived epithelial cells from...
Mammary cancer incidence varies greatly across species and underlying mechanisms remain elusive. We previously showed that mammosphere-derived epithelial cells from species with low mammary cancer incidence, such as horses, respond to carcinogen 7, 12-Dimethylbenz(a)anthracene-induced DNA damage by undergoing apoptosis, a postulated anti-cancer mechanism. Additionally, we found that miR-214-3p expression in mammosphere-derived epithelial cells is lower in mammary cancer-resistant as compared to mammary cancer-susceptible species. Here we show that increasing miR-214 expression and decreasing expression of its target gene nuclear factor kappa B subunit 1 in mammosphere-derived epithelial cells from horses abolishes 7,12-Dimethylbenz(a)anthracene-induced apoptosis. A direct interaction of miR-214-3p with another target gene, unc-5 netrin receptor A, is also demonstrated. We propose that relatively low levels of miR-214 in mammosphere-derived epithelial cells from mammals with low mammary cancer incidence, allow for constitutive gene nuclear factor kappa B subunit 1 expression and apoptosis in response to 7, 12-Dimethylbenz(a)anthracene. Better understanding of the mechanisms regulating cellular responses to carcinogens improves our overall understanding of mammary cancer resistance mechanisms.
Topics: Animals; Horses; Carcinogens; 9,10-Dimethyl-1,2-benzanthracene; NF-kappa B; Epithelial Cells; MicroRNAs; Apoptosis; Anthracenes; Mammals; Neoplasms
PubMed: 37789172
DOI: 10.1038/s42003-023-05370-4 -
Nutrients Jan 2023Traditionally, Curcuma xanthorriza (CX), black cumin seed (BC), and honey have been used by the Indonesian people as medicinal ingredients to treat various health...
Herbal Honey Preparations of Curcuma Xanthorriza and Black Cumin Protect against Carcinogenesis through Antioxidant and Immunomodulatory Activities in Sprague Dawley (SD) Rats Induced with Dimethylbenz(a)anthracene.
BACKGROUND
Traditionally, Curcuma xanthorriza (CX), black cumin seed (BC), and honey have been used by the Indonesian people as medicinal ingredients to treat various health symptoms. CX extracts and BC have been proven in the laboratory as chemopreventive agents, antioxidants, and immunomodulators. In this study, we developed CX extract, BC oil, and honey into herbal honey preparations (CXBCH) and hypothesized that the preparations show chemopreventive activity. The purpose of the study was to determine the CXBCH potential as chemopreventive, antioxidant, and immunomodulatory.
METHOD
In this experimental laboratory research, antioxidant, immunomodulatory, and cytotoxic activities were tested on human mammary cancer cell lines (T47D cells) while the chemopreventive activity of the CXBCH preparations on Sprague Dawley (SD) rats induced with dimethylbenzene(a)anthracene (DMBA).
RESULTS
CXBCH preparations demonstrated immunomodulatory, antioxidant, and cytotoxic activities in T47D, Hela, and HTB-183 cells and in DMBA-induced SD rats, as the preparations inhibited tumor nodule formation, increased the number of CD4, CD8 and CD4CD25 cells, and glutathione-S-transferase (GST) activity, and decreased serum NO levels.
CONCLUSIONS
CXBCH preparations display chemopreventive, antioxidant, and immunomodulatory properties.
Topics: Rats; Animals; Humans; Rats, Sprague-Dawley; Antioxidants; 9,10-Dimethyl-1,2-benzanthracene; Curcuma; Honey; Nigella sativa; Carcinogenesis; Anthracenes; Mammary Neoplasms, Experimental; Carcinogens
PubMed: 36678242
DOI: 10.3390/nu15020371 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... Jan 2024This paper aims to explore the inhibitory effect of Yueju Pills on breast cancer and decipher the underlying mechanism. A total of 92 SPF-grade SD female rats were...
This paper aims to explore the inhibitory effect of Yueju Pills on breast cancer and decipher the underlying mechanism. A total of 92 SPF-grade SD female rats were involved in this study, and 14 of them were randomly selected into control group. The remaining 78 rats were administrated with 7,12-dimethylbenzanthracene(DMBA) by gavage to establish the breast cancer model. The modeled rats were randomized into model, tamoxifen(1.9 mg·kg~(-1)·d~(-1)), and low-and high-dose(17, 34 g·kg~(-1)·d~(-1)) Yueju Pills groups. The mental state, food intake, and activities of the rats were observed daily, and the body weight was measured on alternate days. After 12 weeks of administration, the rats were sacrificed and the tumor weight was measured. The serum estrogen and progeste-rone levels were determined by enzyme-linked immunosorbent assay. The histopathological changes of the breast and tumor were observed by hematoxylin-eosin staining. Western blot was employed to measure the protein levels of glucose transporter 1(GLUT1), lactate dehydrogenase A(LDHA), phosphofructokinase muscle(PFKM), pyruvate kinase isozyme type M2(PKM2), hexokinase 2(HK2), nuclear factor-kappaB(NF-κB), and phosphorylated NF-κB. The intestinal microbiome was examined by 16S rRNA high-throughput sequencing. The results showed that compared with the model group, high and low-dose Yueju Pills showed the tumor inhibition rate of 15.8% and 64.5%, respectively, and the low dose group had stronger inhibitory effect. Compared with the control group, the model group presented elevated the levels of estrogen and progesterone in serum. The administration of Yueju Pills lowered such ele-vation, and the low-dose group showed stronger lowering effect(P<0.05). Compared with the model group, Yueju Pills reduced the glands with increased breast tissue, the degree of breast duct expansion, the number and area of acinar cavity, the secretions, and the layers of mammary epithelial cells. Furthermore, Yueju Pills down-regulated the expression of GLUT1, LDHA, PFKM, PKM2, HK2, and NF-κB(P<0.05) and altered the diversity, composition, structure, and abundance of intestinal flora. The results showed that Yueju Pills could inhibit breast cancer by regulating the secretion of estrogen and progesterone, glycolysis, inflammatory cytokines, and intestinal flora.
Topics: Rats; Female; Animals; 9,10-Dimethyl-1,2-benzanthracene; NF-kappa B; Progesterone; Glucose Transporter Type 1; RNA, Ribosomal, 16S; Neoplasms; Estrogens
PubMed: 38403319
DOI: 10.19540/j.cnki.cjcmm.20230919.401 -
Evaluation of the chemopreventive effects of Hypericum perforatum L on DMBA-applied rat oral mucosa.Archives of Oral Biology Jul 2021Hypericum perforatum L also known as St. John's wort is known to have many beneficial properties for the organism including its antioxidant and anticancer activities. It...
OBJECTIVE
Hypericum perforatum L also known as St. John's wort is known to have many beneficial properties for the organism including its antioxidant and anticancer activities. It is also known to have shown antiproliferative and cytotoxic effects against various cancer cell lines. The purpose of this study was to investigate the effects of Hypericum perforatum L on 7,12-dimethylbenz(a)anthracene-induced rat oral squamous cell carcinoma model.
DESIGN
The in vitro antioxidant properties of Hypericum perforatum L was determined and an extract was prepared. Thirty Wistar male rats were divided randomly into 4 groups (Control group, DMBA group, HP + DMBA group, HP group). The antioxidant defense mechanisms in tissue and blood samples were evaluated biochemically and immunohistochemically, the carcinomatous changes in connective tissue were investigated immunohistochemically and epithelial changes in the tissue samples were evaluated histopathologically.
RESULTS
The extract revealed inhibitory effects on some antioxidant enzymes (catalase, glutathione peroxidase). Immunohistochemical evaluations revealed no invasive changes in the connective tissue. Hypericum perforatum L demonstrated chemopreventive effects although it did not prevent carcinomatous changes altogether.
CONCLUSIONS
Hypericum perforatum L is a promising chemopreventive agent and further studies are needed in order to evaluate the full potential of this plant.
Topics: Animals; Carcinoma, Squamous Cell; Hypericum; Male; Mouth Mucosa; Mouth Neoplasms; Plant Extracts; Rats; Rats, Wistar
PubMed: 33964648
DOI: 10.1016/j.archoralbio.2021.105139