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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 -
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 -
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 -
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 -
In Vivo (Athens, Greece) 2023Patients with radiation sensitive Fanconi anemia (FA) are presenting with cancers of the oral cavity, oropharynx, and other anatomic locations.
BACKGROUND/AIM
Patients with radiation sensitive Fanconi anemia (FA) are presenting with cancers of the oral cavity, oropharynx, and other anatomic locations.
MATERIALS AND METHODS
Animal models for cancer in FA mice used orthotopic tumors from wild type mice. We derived a cancer cell line from Fanca-/- mice by topical application of the chemical carcinogen dimethyl benzanthracene (DMBA).
RESULTS
A Fanca-/- mouse rhabdomyosarcoma was derived from a Fanca-/- (129/Sv) mouse. The in vitro clonogenic survival of the Fanca-/- clone 6 cancer cell line was consistent with the FA genotype. Transplanted tumors demonstrated hypoxic centers surrounded by senescent cells.
CONCLUSION
This Fanca-/- mouse syngeneic cancer should provide a valuable resource for discovery and development of new normal tissue radioprotectors for patients with FA and cancer.
Topics: Humans; Mice; Animals; Fanconi Anemia; Cell Line; Carcinogens; Neoplasms; Fanconi Anemia Complementation Group A Protein
PubMed: 37905617
DOI: 10.21873/invivo.13347 -
Asian Pacific Journal of Cancer... May 2020Most of breast cancer patients are estrogen receptor alpha-positive and have high resistance and side effect of chemotherapeutic drug. Therefore, discovering an...
BACKGROUND
Most of breast cancer patients are estrogen receptor alpha-positive and have high resistance and side effect of chemotherapeutic drug. Therefore, discovering an effective anticancer agent is needed. This research explored the effect of (E)-1-(4'-aminophenyl)-3-phenylprop-2-en-1-one (APE) on miR-18a, Dicer1, and MMP-9 expressions.
METHODS
Twenty four female Sprague-Dawley rats were invetigated in this study. The rats were divided into 6 groups of 4. G1 was considered as normal rat. G2, G3, T1, T2, and T3 were given DMBA 20 mg/kgBW twice a week for 5 weeks to induce mammary cancer. After being affiliated with cancer, G2 was given vehicle and G3 was treated with tamoxifen. T1, T2, and T3 were treated with APE intraperitoneally everyday for 21 days at doses of 5, 15, and 45 mg/kgBW/day, respectively. Blood plasma was collected to measure miR-18a expression using qRT-PCR. Mammary tissues were also collected to determine Dicer1 and MMP-9 expressions by using immunohistochemistry.
RESULTS
The results showed significant down-regulation of miR-18a relative expression and up-regulation of Dicer1 expression in G3 and T1 compared to G2 (P<0.05). MMP-9 expression has significant decrease in T1 compared to G2 (P<0.05).
CONCLUSION
APE can decrease miR-18a and MMP-9 expressions and increase Dicer1 expression in rat mammary cancer. Therefore, this compound could be a candidate of novel anticancer.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Aniline Compounds; Animals; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Carcinogens; Cell Proliferation; Chalcone; DEAD-box RNA Helicases; Female; Gene Expression Regulation, Neoplastic; Mammary Neoplasms, Experimental; Matrix Metalloproteinase 9; Mice; MicroRNAs; Propiophenones; Rats, Sprague-Dawley; Ribonuclease III; Tumor Cells, Cultured
PubMed: 32458624
DOI: 10.31557/APJCP.2020.21.5.1213 -
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 -
Current Cancer Drug Targets 2024The aim of this study is to examine the protective properties of and against the development of skin cancer.
AIM
The aim of this study is to examine the protective properties of and against the development of skin cancer.
METHODS
The skin cancer balb/c mouse model was utilized in the study. Plant extracts were administered to animals using oral gavage. In addition, skin cancer was induced using 7,12-dimethylbenz( a) anthracene (DMBA).
RESULTS
The study found that extract reduced both tumor incidence (P<0.01) and papilloma frequency (<0.001) and delayed the onset of tumor development (<0.001). The extract did not affect tumor size in animals. leaf extract reduced the number of tumors per animal, the incidence of tumors, and the frequency of papilloma (<0.05). In addition, it delayed (<0.01) the onset of tumors. Treatment of animals with seed extract reduced the frequency of papilloma (P<0.05) and delayed the onset of tumors (<0.05). However, the examined plant extracts did not impact the size of tumors induced by DMBA (>0.05).
CONCLUSION
The findings of this study revealed that and could protect against cancer development as indicated using the animal model of skin painting assay.
Topics: Animals; Coriandrum; Plant Extracts; Mice, Inbred BALB C; Mice; 9,10-Dimethyl-1,2-benzanthracene; Skin Neoplasms; Female; Plant Leaves; Male; Disease Models, Animal
PubMed: 37592785
DOI: 10.2174/1568009623666230817101757 -
Cytokine Nov 2019Cancer is a high-impact disease throughout the world. A negative correlation has been established between the development of cancer and the Th2 immune response....
BACKGROUND
Cancer is a high-impact disease throughout the world. A negative correlation has been established between the development of cancer and the Th2 immune response. Infection by helminth parasites is characterized by the induction of a strong and long-lasting Th2 response. The aim of this work was to evaluate the effect of the immune response induced by the infection with the helminth Hymenolepis nana, on the tumorigenesis induced by dimethylbenz-anthracene (DMBA) in mice.
METHODOLOGY
Four different groups of 14 female BALB/c mice were formed; Group A, dimethyl sulfoxide (DMSO) (vehicle) was administered cutaneously, Group B infected with H. nana, group C, cutaneously DMBA and finally Group D infected with H. nana and cutaneous DMBA. The tumor load was determined in those animals that developed cancerous lesions. In all groups were determined: serum concentration of IgE, IFNγ, IL-10, IL-5 and malondialdehyde (MDA). The inflammatory infiltrate was analyzed from skin samples and the expression of the main eosinophilic protein and myeloperoxidase was determined.
RESULTS
The group previously infected with H. nana had a reduced amount of tumors with smaller size, in comparison to the group that received only DMBA; this reduction was associated with lower levels of IFNγ and IL-10, while levels of IgE, IL-5 and MDA were higher. Further, the number of eosinophils and neutrophils was statistically higher in the animals that were previously infected with the helminth and developed less tumors.
CONCLUSION
The immune response induced by H. nana infection is associated with the reduction of tumors probably due to the activity of eosinophils and neutrophils.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogenesis; Cytokines; Female; Hymenolepiasis; Hymenolepis nana; Mice; Mice, Inbred BALB C; Th2 Cells
PubMed: 31255915
DOI: 10.1016/j.cyto.2019.154743