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Molecules (Basel, Switzerland) Jul 2020essential oil and carvacrol have shown an antitumor effect on breast tumor cell lines; the main objective of this research was to evaluate the antitumor effect of the...
essential oil and carvacrol have shown an antitumor effect on breast tumor cell lines; the main objective of this research was to evaluate the antitumor effect of the essential oil of (EOCc) and carvacrol on 7,12-dimethylbenz [a] anthracene (DMBA)-induced breast cancer in female rats. Cancer was induced by a single administration of DMBA at dose of 80 mg/kg body weight (BW). A total of 54 female Holtzman rats were randomly assigned into 9 groups (n = 6). Group I: PS (Physiological saline); Group II: DMBA; Groups III, IV, and V: DMBA + EOCc at doses of 50, 100 and 200 mg/kg/day BW, respectively; Groups VI, VII, and VIII: DMBA + carvacrol at doses of 50, 100 and 200 mg/kg/day BW, respectively; and group IX: DMBA + EOCc + carvacrol at doses of 100 mg/kg/day BW. The treatment lasted 14 weeks. As results, EOCc showed a reduction in tumors as well as necrosis and mitosis. Animals treated with carvacrol did not show necrosis, mitosis, or infiltration. Carvacrol at dose of 100 mg/kg/day BW revealed a significant decrease in the cumulative tumor volume down to 0.11 ± 0.05 cm compared to 0.38 ± 0.04 cm of the DMBA group ( < 0.01). It is concluded that EOCc and carvacrol had an antitumor effect on DMBA-induced breast cancer in female rats.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antioxidants; Biphenyl Compounds; Body Weight; Carcinogenesis; Cymbopogon; Cymenes; Female; Mammary Neoplasms, Experimental; Oils, Volatile; Picrates; Rats, Sprague-Dawley
PubMed: 32698395
DOI: 10.3390/molecules25143284 -
The Journal of Investigative Dermatology Feb 2021Nonmelanoma skin cancer such as cutaneous squamous cell carcinoma (cSCC) is the most common form of cancer and can occur as a consequence of DNA damage to the epithelium...
Nonmelanoma skin cancer such as cutaneous squamous cell carcinoma (cSCC) is the most common form of cancer and can occur as a consequence of DNA damage to the epithelium by UVR or chemical carcinogens. There is growing evidence that the complement system is involved in cancer immune surveillance; however, its role in cSCC remains unclear. Here, we show that complement genes are expressed in tissue from patients with cSCC, and C3 activation fragments are present in cSCC biopsies, indicating complement activation. Using a range of complement-deficient mice in a two-stage mouse model of chemically-induced cSCC, where a subclinical dose of 7,12-dimethylbenz[a]anthracene causes oncogenic mutations in epithelial cells and 12-O-tetradecanoylphorbol-13-acetate promotes the outgrowth of these cells, we found that C3-deficient mice displayed a significantly reduced tumor burden, whereas an opposite phenotype was observed in mice lacking C5aR1, C5aR2, and C3a receptor. In addition, in mice unable to form the membrane attack complex, the tumor progression was unaltered. C3 deficiency did not affect the cancer response to 7,12-dimethylbenz[a]anthracene treatment alone but reduced the epidermal hyperplasia during 12-O-tetradecanoylphorbol-13-acetate-induced inflammation. Collectively, these data indicate that C3 drives tumorigenesis during chronic skin inflammation, independently of the downstream generation of C5a or membrane attack complex.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma, Squamous Cell; Complement Activation; Complement C3; Complement C5; Complement Membrane Attack Complex; Disease Models, Animal; Disease Progression; Humans; Mice; Mice, Knockout; Mice, Transgenic; Neoplasms, Experimental; Receptor, Anaphylatoxin C5a; Receptors, Complement; Signal Transduction; Skin; Skin Neoplasms; Tumor Escape
PubMed: 32682912
DOI: 10.1016/j.jid.2020.06.025 -
Cancer Science Aug 2020CENP-50/U is a component of the CENP-O complex (CENP-O/P/Q/R/U) and localizes to the centromere throughout the cell cycle. Aberrant expression of CENP-50/U has been...
CENP-50/U is a component of the CENP-O complex (CENP-O/P/Q/R/U) and localizes to the centromere throughout the cell cycle. Aberrant expression of CENP-50/U has been reported in many types of cancers. However, as Cenp-50/U-deficient mice die during early embryogenesis, its functions remain poorly understood in vivo. To investigate the role of Cenp-50/U in skin carcinogenesis, we generated Cenp-50/U conditional knockout (K14Cre -Cenp-50/U ) mice and subjected them to the 7,12-dimethylbenz(a)anthracene (DMBA)/terephthalic acid (TPA) chemical carcinogenesis protocol. As a result, early-stage papillomas decreased in Cenp-50/U-deficient mice. In contrast, Cenp-50/U-deficient mice demonstrated almost the same carcinoma incidence as control mice. Furthermore, mRNA expression analysis using DMBA/TPA-induced papillomas and carcinomas revealed that Cenp-50/U expression levels in papillomas were significantly higher than in carcinomas. These results suggest that Cenp-50/U functions mainly in early papilloma development and it has little effect on malignant conversion.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogenesis; Carcinogens; Cell Cycle Proteins; Humans; Mice; Mice, Knockout; Neoplasms, Experimental; Papilloma; Phthalic Acids; Skin; Skin Neoplasms
PubMed: 32535988
DOI: 10.1111/cas.14533 -
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 -
Life Sciences Aug 2020Ovarian cancer (OC) is the most lethal gynecological malignancies and many women develop chemoresistance associated with the inflammatory process. We investigated the...
AIMS
Ovarian cancer (OC) is the most lethal gynecological malignancies and many women develop chemoresistance associated with the inflammatory process. We investigated the effects of P-MAPA and IL-12 on the inflammatory and immune responses in a chemically-induced OC model.
MAIN METHODS
OCs were induced with 7,12-dimethylbenz(a)anthracene into the ovarian bursa, and the animals were given P-MAPA (5 mg/kg bw., i.p., twice a week), or IL-12 (300 ng/kg bw., i.p., one a week) for 60 days, or both P-MAPA and IL-12. Immunohistochemistry, western blot, flow cytometry, and multiplex assay were used to examine the effectiveness of immunotherapies in OC.
KEY FINDINGS
The combinatory therapy improved the general OC features, reducing inflammatory cells and adipocyte accumulation, in addition to revealing a soft and mobile tissue with no adherences and peritoneal implants. P-MAPA treatment increased the levels of TLR2, TLR4 and TRIF in OCs while decreasing the number of regulatory T (Treg) cells. Additionally, the association of P-MAPA with IL-12 significantly increased the number of CD4+ and CD8+ T effector cells in draining lymph nodes. Regarding the inflammatory mediators, P-MAPA enhanced the levels of the pro-inflammatory cytokine IL-17 while P-MAPA+IL-12 increased the levels of IL-1β. Treatment with IL-12 enhanced the cytokine levels of IL-17, TNF-α, IL-1β, and IL-2 in addition to the chemokine MIP-1α.
SIGNIFICANCE
We conclude that P-MAPA upregulated TLR2 and TLR4 signaling, possibly activating the non-canonical pathway, while attenuating the tumor immunosuppression. Also, the combination of P-MAPA with IL-12 improves the antitumor immunoresponse, opening a new therapeutic approach for fighting OC.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Adaptor Proteins, Vesicular Transport; Adipocytes; Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chemokine CCL3; Cytokines; Drug Synergism; Female; Inflammation; Interleukin-12; Linoleic Acids; Oleic Acids; Ovarian Neoplasms; Rats; T-Lymphocytes, Regulatory; Toll-Like Receptor 2; Toll-Like Receptor 4
PubMed: 32433918
DOI: 10.1016/j.lfs.2020.117786 -
The Journal of Investigative Dermatology Oct 2020We previously revealed the crucial roles of a chemokine, CX3CL1, and its receptor, CX3CR1, in skin wound healing. Although repeated wounds frequently develop into skin...
We previously revealed the crucial roles of a chemokine, CX3CL1, and its receptor, CX3CR1, in skin wound healing. Although repeated wounds frequently develop into skin cancer, the roles of CX3CL1 in skin carcinogenesis remain elusive. Here, we proved that CX3CL1 protein expression and CX3CR1 macrophages were observed in human skin cancer tissues. Similarly, we observed the enhancement of CX3CL1 expression and the abundant accumulation of CX3CR1 tumor-associated macrophages with M2-like phenotypes in the skin carcinogenesis process induced by the combined treatment with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. In this mouse skin carcinogenesis process, CX3CR1 tumor-associated macrophages exhibited M2-like phenotypes with the expression of Wnt3a and angiogenic molecules including VEGF and matrix metalloproteinase 9. Compared with wild-type mice, CX3CR1-deficient mice showed fewer numbers of skin tumors with a lower incidence. Concomitantly, M2-macrophage numbers and neovascularization were reduced with the depressed expression of angiogenic factors and Wnt3a. Thus, the CX3CL1-CX3CR1 axis can crucially contribute to skin carcinogenesis by regulating the accumulation and functions of tumor-associated macrophages. Thus, this axis can be a good target for preventing and/or treating skin cancers.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; CX3C Chemokine Receptor 1; Cell Movement; Chemokine CX3CL1; Humans; Male; Mice; Mice, Inbred C57BL; Skin Neoplasms; Tetradecanoylphorbol Acetate; Tumor-Associated Macrophages; Wnt3A Protein
PubMed: 32179066
DOI: 10.1016/j.jid.2020.02.023 -
BioMed Research International 2020To investigate the effect of systemic administration of the immunosuppressant dexamethasone (DM) while inducing hamster buccal pouch DMBA carcinogenesis. . Two different...
OBJECTIVES
To investigate the effect of systemic administration of the immunosuppressant dexamethasone (DM) while inducing hamster buccal pouch DMBA carcinogenesis. . Two different experiments were performed. In the first experiment, hamsters' right buccal pouches in group A ( = 10) were painted three times per week with 7,12-dimethylbenzanthracene (DMBA) 0.5%, while pouches of animals in group B ( = 10) were painted three times per week with 7,12-dimethylbenzanthracene (DMBA) 0.5%, while pouches of animals in group B (.
RESULTS
The time of macroscopic neoplasm development was reduced when DM-DMBA coexposition was employed, finding tumors after 10-12 weeks of exposition. In addition, the frequency of histopathological lesions was higher.
CONCLUSION
Immunomodulatory action of dexamethasone may reduce the time of oral squamous cell carcinoma (OSCC) induction and may increase the incidence of neoplasms developed.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma, Squamous Cell; Cricetinae; Dexamethasone; Male; Mesocricetus; Mouth Mucosa; Mouth Neoplasms
PubMed: 32149076
DOI: 10.1155/2020/1470868 -
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 -
Experimental Biology and Medicine... Feb 2020-mannose-sensitive hemagglutinin (PAM) is an inactivate with mannose-sensitive hemagglutinin. Recently, the anticancer properties of PAM against many cancers have been...
UNLABELLED
-mannose-sensitive hemagglutinin (PAM) is an inactivate with mannose-sensitive hemagglutinin. Recently, the anticancer properties of PAM against many cancers have been reported across a range of studies. However, the exact mechanism through which PAM prevents skin cancer remains unclear. The aim of this study is to show to what extent PAM could inhibit the dimethylbenzanthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin cancer. JB6 cells were treated by TPA so as to establish an model. The effects of PAM on proliferation of the cells were analyzed using cell counting kit-8 assays. Effects on epithelial–mesenchymal transition (EMT) were assayed by real-time PCR and Western blotting. A DMBA/TPA-induced skin cancer mouse model was also established. The results showed that TPA promoted EMT changes through the activation of the hedgehog (Hh) pathway, which was reversed by PAM. Moreover, PAM inhibited the cancer growth and Hh pathway . These data indicate that PAM may serve as a potential anticancer agent for the treatment of skin cancer.
IMPACT STATEMENT
-mannose-sensitive hemagglutinin (PAM) restrained the chemical-induced skin cancer cells and partly through suppressing the Hh signaling pathway, indicating that PAM may be a promising anticancer agent for treating skin cancer.
Topics: Epithelial-Mesenchymal Transition; Fimbriae Proteins; Hedgehog Proteins; Hemagglutinins; Humans; Mannose; Pseudomonas aeruginosa; Skin Neoplasms
PubMed: 31903775
DOI: 10.1177/1535370219897240 -
Acta Cirurgica Brasileira 2019To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced...
PURPOSE
To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced breast cancer model in Wistar rats.
METHODS
We compared the response of breast cancer to the oral administration of A. chica extract (ACE) for 16 weeks, associated or not with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500μg/kg injected i.p; DMBA+ACE+Vincristine 250μg/kg i.p. Imaging by microPET and fluorescence, biochemistry, oxidative stress, hematology and histopathology were used to validate the treatments.
RESULTS
All animals survived. A gradual weight gain in all groups was observed, with no significant difference (p>0.05). The oral administration of ACE and ACE+vincristine 50% significantly reduced breast tumors incidence examined with PET-18FDG and fluorescence (p<0.001). Significant reduction of serum transaminases, oxidative stress and hematological toxicity were observed in these groups. Antioxidant enzyme levels in breast tissue were significantly higher compared to the DMBA and DMBA+vincristine groups.
CONCLUSION
These results demonstrate for the first time that ACE positively influences the treatment of DMBA-induced breast cancer in animal model, inducing a reduction in oxidative stress and chemotherapy toxicity, meaning that ACE may have clinical implication in further studies.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents; Bignoniaceae; Breast Neoplasms; Carcinogens; Carcinoma; Catalase; Female; Fluorodeoxyglucose F18; Glutathione Peroxidase; Neoplasms, Experimental; Optical Imaging; Oxidative Stress; Plant Extracts; Positron-Emission Tomography; Radiopharmaceuticals; Rats, Wistar; Reproducibility of Results; Superoxide Dismutase; Time Factors; Treatment Outcome; Vincristine
PubMed: 31826147
DOI: 10.1590/s0102-865020190100000001