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Foods (Basel, Switzerland) Jan 2023The aim of the study was to evaluate the effect of selected polyphenolic compounds: epicatechin, apigenin, and naringenin, administered separately or in combination with...
The aim of the study was to evaluate the effect of selected polyphenolic compounds: epicatechin, apigenin, and naringenin, administered separately or in combination with zinc (Zn), on the growth and development of the neoplastic process induced by 7,12-dimethylbenz[a]anthracene (DMBA) in rats. The impact of supplementation with the above-mentioned compounds on the content of modified derivatives: 1-methyladenosine, N6-methyl-2'-deoxyadenosine, O-methylguanosine, 7-methylguanine, 3-methyladenine, 1-methylguanine, 2-amino-6,8-dihydroxypurine, and 8-hydroxy-2'-deoxyguanosine in the urine of rats with mammary cancer was also assessed. Female Sprague-Dawley rats divided into 7 groups were used in the study: animals without supplementation and animals supplemented with apigenin, epicatechin, and naringenin separately or in combination with zinc. To induce mammary cancer, rats were treated with DMBA. Modified derivatives were determined by a validated high-performance liquid chromatography coupled to mass spectrometry method. Based on the obtained results, it can be said that supplementation of the animals with naringenin inhibits the development and progression of the neoplastic process in rats treated with 7,12-dimethylbenzanthracene. Neoplastic tumors were found in only 2 of 8 rats (incidence: 25%) and were considered to be at most grade 1 malignancy. The first palpable tumors in the group of animals receiving naringenin appeared two-three weeks later when compared to other groups. The combination of zinc with flavonoids (apigenin, epicatechin, and naringenin) seems to stimulate the process of carcinogenesis. The level of N6-methyl-2'-deoxyadenosine and 3-methyladenine in the urine of rats was statistically significantly higher in the groups supplemented with apigenin, epicatechin, and naringenin administered in combination with Zn than in the groups receiving only polyphenolic compounds. In conclusion, supplementation of rats with selected flavonoids administered separately or in combination with Zn has an impact on the development of neoplasms and the level of modified nucleosides in the urine of rats with breast cancer. Our results raise the question of whether simultaneous diet supplementation with more than one anti-cancer agent may reduce/stimulate the risk of carcinogenesis.
PubMed: 36673448
DOI: 10.3390/foods12020356 -
Nutrition and Cancer 2022(ZO) and (TC) are plants used for the treatment of diverse illnesses in traditional medicine. The present study investigates the preventive effect of - extract (ZOTC)...
(ZO) and (TC) are plants used for the treatment of diverse illnesses in traditional medicine. The present study investigates the preventive effect of - extract (ZOTC) against DMBA-induced breast cancer in a rat model. Bioactive compounds from ZO (6-gingerol, 6-shogaol) and TC (gallic acid, ellagic acid, corilagin, chebulinic acid, and chebulagic acid) were detected using high-performance liquid chromatography. Mammary carcinogenesis was induced in rats with a single subcutaneous injection of 7,12-Dimethylbenz[a]anthracene (DMBA). Oral administration of ZOTC ameliorated the antioxidant status in mammary tissues, serum lipid levels, and serum cytokines. Histological analysis of the mammary tissue (normal and tumor) was carried out to obtain pathological alterations due to ZOTC treatment. The effect of ZOTC on the mechanistic target of rapamycin (mTOR) gene and accumulation of corresponding gene product was also investigated. mTOR plays a central role in cell metabolism and proliferation in normal and cancer cells. Transcriptional and immunohistochemical analysis showed the downregulation of mTOR expression in the mammary tissues of ZOTC-treated rats. In conclusion, the results obtained suggest that ZOTC can suppress tumor progression in DMBA-induced breast cancer rats inhibition of the mTOR pathway.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Ellagic Acid; Zingiber officinale; Mammary Neoplasms, Experimental; Plant Extracts; Rats; TOR Serine-Threonine Kinases; Terminalia
PubMed: 33821702
DOI: 10.1080/01635581.2021.1903948 -
Journal of Biochemical and Molecular... Oct 2019Breast cancer is a prevalent of tumoregenesis in women and reports for the maximum mortality and morbidity in the global. Ginger (Zingiber officinale) is the mainly...
Breast cancer is a prevalent of tumoregenesis in women and reports for the maximum mortality and morbidity in the global. Ginger (Zingiber officinale) is the mainly widespread spice and herbal remedies used in the world. Since antique periods, ginger has been used in Greece, India and China for the curing of upset stomach, nausea, diarrhea, colds, and headaches. The current work was planned to explore the anticancer properties of zingerone (ZO) toward 7,12-dimethylbenz(a)anthracene (DMBA)-treated mammary carcinogenesis in Sprague-Dawley (SD) rats and MCF-7 mammary cancer cells. The mammary carcinogenesis was produced through a single dosage of DMBA (20 mg/kg bwt) mixed in soya oil (1 mL) administrated intragastrically with a gavage. We found improved concentrations of lipid peroxidation (LOOH and TBARS), carcinoembryonic antigen, lowered levels of enzymatic (CAT, GPx, and SOD), and nonenzymatic (vitamin E, GSH, and vitamin C) antioxidant in mammary tissues and plasma of DMBA-induced cancer bearing animals. Moreover, augmented concentrations of phase I (Cyt-b and CYP ) and reduced levels of phase II (GR and GST) detoxification microsomal proteins in mammary tissues were noticed. ZO administrations significantly reverted back to all these parameters in this way, showing efficient of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of ZO were noticed loss of cell viability, improved reactive oxygen species formation, and reduced MMP. Furthermore, the status of apoptosis proteins such as Bcl-2, Bax, and Bid expressions was determined by using Western blot analysis techniques. Overall, these results proposed the anticancer effect of ZO toward DMBA-induced mammary cancer in SD animals and Michigan cancer foundation-7 mammary cancer cells.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; Biotransformation; Blotting, Western; Carcinogens; Caspases; Guaiacol; Humans; Lipid Peroxidation; MCF-7 Cells; Mammary Neoplasms, Experimental; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species
PubMed: 31476248
DOI: 10.1002/jbt.22387 -
Anticancer Research Mar 2021Microsomal prostaglandin (PG) E synthase-1 (mPGES-1) is a terminal enzyme in PGE synthesis and highly expressed in several cancers. In this study, to reveal the...
BACKGROUND/AIM
Microsomal prostaglandin (PG) E synthase-1 (mPGES-1) is a terminal enzyme in PGE synthesis and highly expressed in several cancers. In this study, to reveal the involvement of mPGES-1 in skin carcinogenesis, the effect of mPGES-1 deficiency on two-stage skin carcinogenesis in mice was investigated.
MATERIALS AND METHODS
A two-stage skin carcinogenesis model using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter was applied on mPGES-1 knockout (KO) mice and littermate wild-type mice of a Balb/c genetic background.
RESULTS
DMBA/TPA-induced skin carcinogenesis was suppressed in mPGES-1 KO mice. The induction of IL-17 and other inflammatory cytokines by TPA was also suppressed by mPGES-1 deficiency, although DMBA-induced apoptosis was not affected.
CONCLUSION
mPGES-1 promotes chemically induced skin carcinogenesis and might play an important role in the TPA-induced promotion phase of the two-stage skin carcinogenesis model. mPGES-1 inhibition may be a therapeutic target for skin cancer.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; Cyclooxygenase 2; Cytokines; Dinoprostone; Mice; Mice, Inbred BALB C; Prostaglandin-E Synthases; Skin Neoplasms; Tetradecanoylphorbol Acetate
PubMed: 33788722
DOI: 10.21873/anticanres.14888 -
Pakistan Journal of Pharmaceutical... May 2021The current study investigated the prospective effect of Silybum marianum L. and Eucalyptus camaldulensis Dehnh extracts against skin cancer. Skin cancer was induced by...
The current study investigated the prospective effect of Silybum marianum L. and Eucalyptus camaldulensis Dehnh extracts against skin cancer. Skin cancer was induced by 7,12-dimethylbenz(a) anthracene (DMBA) in young Balb/c mice. Plant extracts were administered to animals orally, once/day (100mg/kg, 5 days/week) for the 20 weeks. Anticancer activity was examined via tumor progression, where antimutagenic activity was measured using 8-OHdG and sister chromatid exchange (SCE) levels. Eucalyptus camaldulensis Dehnh. leaves extract and Silybum marianum L. leaves extract significantly reduced 8-OHdG in cultured human lymphocytes in a dose-response manner (P<0.05). Similarly, the leave extracts of both plants significantly reduced chromosomal damage as measured by SCE levels (P<0.05). In the skin painting assay, the leave extracts of both plants significantly delayed the onset of tumors compared to DMBA treated group (P<0.05). The Silybum marianum leaves extract significantly reduced tumor incidence (P<0.01) and papilloma frequency (P<0.01) induced by DMBA. The Eucalyptus camaldulensis leaves extract significantly reduced the number of tumors per animal (P<0.05) and incidence of tumors (P<0.001). The in vitro and in vivo findings showed that leaves of Silybum marianum L. and Eucalyptus camaldulensis Dehnh. extracts might be a promising source for anticancer and antimutagenic agents against human cancer.
Topics: 8-Hydroxy-2'-Deoxyguanosine; 9,10-Dimethyl-1,2-benzanthracene; Animals; Antimutagenic Agents; Carcinogens; Carcinoma; Cell Proliferation; Drug Screening Assays, Antitumor; Eucalyptus; Humans; In Vitro Techniques; Lymphocytes; Mice; Silybum marianum; Oxidative Stress; Plant Extracts; Plant Leaves; Skin; Skin Neoplasms; Tumor Burden
PubMed: 34602423
DOI: No ID Found -
Journal of Visualized Experiments : JoVE Dec 2019Cancer is one of the most devastating human diseases. Experimental cancer models are important to gain insight into the complex interplay of different cell types and...
Cancer is one of the most devastating human diseases. Experimental cancer models are important to gain insight into the complex interplay of different cell types and genes in promoting tumor progression and to provide a platform for testing the efficacy of different therapeutic approaches. One of the most commonly used experimental inflammatory cancer models is the DMBA-TPA two-stage skin carcinogenesis model. Tumor formation is induced in this model by the topical application of two different chemicals, 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoyl phorbol-13-acetate (TPA), that together cause papilloma formation in the skin. As the primary outcome is papilloma formation in the skin, the model is an ideal, reliable, and reproducible way to address both tumor initiation (tumor-free survival) and tumor progression (number and size of visible tumors). The effects of the DMBA-TPA treatment are transmitted via an inflammatory mechanism, which makes this model especially suitable for studying the role of the immune system in tumor formation. However, this model is restricted to the skin and other surfaces where the chemicals can be applied on. A detailed protocol is provided in this article to use the model successfully.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogenesis; Carcinogens; Female; Humans; Skin Neoplasms; Tetradecanoylphorbol Acetate
PubMed: 31904021
DOI: 10.3791/60445 -
BMC Complementary Medicine and Therapies Aug 2023Açaí, a Brazilian native fruit, has already been demonstrated to play a role in the progress of breast cancer and cardiotoxicity promoted by chemotherapy agents. Thus,...
BACKGROUND
Açaí, a Brazilian native fruit, has already been demonstrated to play a role in the progress of breast cancer and cardiotoxicity promoted by chemotherapy agents. Thus, the present study aimed to evaluate the combined use of açaí and the FAC-D chemotherapy protocol in a breast cancer model in vivo.
METHODS
Mammary carcinogenesis was induced in thirty female Wistar rats by subcutaneous injection of 25 mg/kg 7,12-dimethylbenzanthracene (DMBA) in the mammary gland. After sixty days, the rats were randomized into two groups: treated with 200 mg/kg of either açaí extract or vehicle, via gastric tube for 45 consecutive days. The FAC-D protocol was initiated after 90 days of induction by intraperitoneal injection for 3 cycles with a 7-day break each. After treatment, blood was collected for haematological and biochemical analyses, and tumours were collected for macroscopic and histological analyses. In the same way, heart, liver, and kidney samples were also collected for macroscopic and histological analyses.
RESULTS
Breast cancer was found as a cystic mass with a fibrotic pattern in the mammary gland. The histological analysis showed an invasive carcinoma area in both groups; however, in the saline group, there was a higher presence of inflammatory clusters. No difference was observed regarding body weight, glycaemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and urea in either group. However, açaí treatment decreased creatine kinase (CK), creatine kinase MB (CKMB), troponin I and C-reactive protein levels and increased the number of neutrophils and monocytes. Heart histopathology showed normal myocardium in the açaí treatment, while the saline group presented higher toxicity effects with loss of architecture of cardiac tissue. Furthermore, the açaí treatment presented greater collagen distribution, increased hydroxyproline concentration and lower H2AX immunostaining in the heart samples.
CONCLUSION
Açaí decreased the number of inflammatory cells in the tumor environment and exhibited protection against chemotherapy drug cardiotoxicity with an increased immune response in animals. Thus, açaí can be considered a promising low-cost therapeutic treatment that can be used in association with chemotherapy agents to avoid heart damage.
Topics: Female; Animals; Rats; Rats, Wistar; Euterpe; Cardiotoxicity; Heart; Creatine Kinase; Neoplasms
PubMed: 37626388
DOI: 10.1186/s12906-023-04104-7 -
International Journal of Cancer Mar 2024Gastrointestinal bacteria are known to have an impact on local and systemic immunity, and consequently either promote or suppress cancer development. Following the...
Gastrointestinal bacteria are known to have an impact on local and systemic immunity, and consequently either promote or suppress cancer development. Following the notion that perinatal bacterial exposure might confer immune system competency for life, we investigated whether early-life administration of cholera-toxin (CT), a protein exotoxin of the small intestine pathogenic bacterium Vibrio cholerae, may shape local and systemic immunity to impart a protective effect against tumor development in epithelia distantly located from the gut. For that, newborn mice were orally treated with low non-pathogenic doses of CT and later challenged with the carcinogen 7,12-dimethylbenzanthracene (DMBA), known to cause mainly mammary, but also skin, lung and stomach cancer. Our results revealed that CT suppressed the overall incidence and multiplicity of tumors, with varying efficiencies among cancer types, and promoted survival. Harvesting mouse tissues at an earlier time-point (105 instead of 294 days), showed that CT does not prevent preneoplastic lesions per se but it rather hinders their evolution into tumors. CT pretreatment universally increased apoptosis in the cancer-prone mammary, lung and nonglandular stomach, and altered the expression of several cancer-related molecules. Moreover, CT had a long-term effect on immune system cells and factors, the most prominent being the systemic neutrophil decrease. Finally, CT treatment significantly affected gut bacterial flora composition, leading among others to a major shift from Clostridia to Bacilli class abundance. Overall, these results support the notion that early-life CT consumption is able to affect host's immune, microbiome and gene expression profiles toward the prevention of cancer.
Topics: Animals; Mice; Cholera Toxin; Weaning; Vibrio cholerae; Carcinogenesis; Neoplasms
PubMed: 38095490
DOI: 10.1002/ijc.34816 -
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 -
Nutrition and Cancer 2021Phytochemicals appeared as a rich source of efficient and safe agents against many diseases like cancer. Various herbal sources are rich in oleanolic acid (OA). The...
Phytochemicals appeared as a rich source of efficient and safe agents against many diseases like cancer. Various herbal sources are rich in oleanolic acid (OA). The scope of this study was to assess the biochemical and molecular mechanisms implicated in the ameliorative potency of OA against DMBA-induced liver carcinogenesis. Forty-eight male albino mice were assigned randomly to five groups (eight mice each) as follows: control healthy group, olive oil group, OA group, DMBA group, and DMBA with OA. Apoptosis, autophagy, inflammation, proliferation, and angiogenesis were investigated in the tissue samples. Histopathological examination was carried out as well as liver enzymes activity and other hepatic antioxidant and inflammatory biomarkers. The treatment with OA effectively suppressed the DMBA-initiated liver carcinogenesis via modulation of antioxidant status, induction of apoptosis and autophagy through modulating the expression of Caspase-3, Bcl-2 and Beclin-1, inhibiting angiogenesis (VEGF), proliferation (PCNA), and improved liver function and histological picture with a reduction in AFP level. Additionally, OA applies its antitumor effects by inhibition of proinflammatory transcription factor NF-κB and inflammatory markers (TNF-α and Cox-2) associated with DMBA administration. The present study shows that OA treatment efficiently suppressed the DMBA-initiated liver carcinogenesis through induction of mitochondrial-mediated apoptosis and autophagy and modulating inflammation.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; Autophagy; Carcinogenesis; Liver; Male; Mice; Oleanolic Acid
PubMed: 32519911
DOI: 10.1080/01635581.2020.1776887