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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 -
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 -
The Journal of Investigative Dermatology Jan 2024
Topics: Animals; Mice; Remission, Spontaneous; Carcinogens; 9,10-Dimethyl-1,2-benzanthracene; Skin Diseases; Skin Neoplasms; Tetradecanoylphorbol Acetate; Skin
PubMed: 37543244
DOI: 10.1016/j.jid.2023.07.004 -
Combinatorial Chemistry & High... 2024Oral squamous cell carcinoma (OSCC) has a poor prognosis when treated with surgery and chemotherapy. Therefore, a new therapy and preventative strategy for OSCC and its...
BACKGROUND
Oral squamous cell carcinoma (OSCC) has a poor prognosis when treated with surgery and chemotherapy. Therefore, a new therapy and preventative strategy for OSCC and its underlying mechanisms are desperately needed. The purpose of this study was to examine the chemopreventive effects of sanggenol L on oral squamous cell carcinoma (OSCC). The research focused on molecular signalling pathways in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis.
AIM
The purpose of this study was to look at the biochemical and chemopreventive effects of sanggenol L on 7,12-dimethylbenz(a)anthracene (DMBA)-induced HBP (hamster buccal pouch) carcinogenesis via cell proliferation and the apoptotic pathway.
METHODS
After developing squamous cell carcinoma, oral tumours continued to progress leftward into the pouch 3 times per week for 10 weeks while being exposed to 0.5 % reactive DMBA three times per week. Tumour growth was caused by biochemical abnormalities that induced inflammation, increased cell proliferation, and decreased apoptosis.
RESULTS
Oral sanggenol L (10 mg/kg bw) supplementation with cancer-induced model DMBApainted hamsters prevented tumour occurrences, improved biochemistry, inhibited inflammatory markers, decreased cell proliferation marker expression of tumour necrosis factor-alpha (TNF- α), nuclear factor (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and induced apoptosis.
CONCLUSION
Sanggenol L could be developed into a new medicine for the treatment of oral carcinogenesis.
Topics: Animals; 9,10-Dimethyl-1,2-benzanthracene; Apoptosis; Cell Proliferation; Mouth Neoplasms; Cricetinae; Signal Transduction; Carcinoma, Squamous Cell; Carcinogenesis; Male; Mesocricetus
PubMed: 37496247
DOI: 10.2174/1386207326666230726140706 -
Journal of Biochemical and Molecular... Oct 2023C-type natriuretic peptide (CNP) exhibits anti-inflammatory activity besides its natriuretic and diuretic functions. The present study aimed to determine the anticancer...
C-type natriuretic peptide (CNP) exhibits anti-inflammatory activity besides its natriuretic and diuretic functions. The present study aimed to determine the anticancer and synergistic therapeutic activity of CNP against a 7,12-Dimethylbenz[a]anthracene (DMBA)/Croton oil-induced skin tumor mouse model. CNP (2.5 µg/kg body weight) was injected either alone and/or in combination with Cisplatin (CDDP) (2 mg/kg body weight) for 4 weeks. The dorsal skin tumor incidences/growth and mortality rate were recorded during the experimental period of 16 weeks. The serum C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels, infiltrating mast cells, and AgNORs proliferating cells count were analyzed in control and experimental mice. Further, the expression profile of marker genes of proliferation, inflammation, and progression molecules were analyzed using Reverse transcriptase-polymerase chain reaction (RT-PCR)/quantitative PCR (qPCR), western blot, and immunohistochemistry. The DMBA/Croton oil-induced mice exhibited 100% tumor incidence. Whereas, CNP alone, CDDP alone, and CNP+CDDP combination-treated mice exhibited 58%, 46%, and 24% tumor incidence, respectively. Also, a marked reduction in the levels of serum CRP and LDH, the number of infiltrating mast cells count and AgNORs proliferating cells count were noticed in the mice skin sections. Further, a significant reduction in both mRNA and protein expression levels of proliferation, inflammation, and progression markers were noticed in CNP (p < 0.01), CDDP (p < 0.01), and CNP+CDDP combination (p < 0.001) treated mice, respectively. The results of the present study suggest that CNP has anticancer activity. Further, the CNP+CDDP treatment has more promising anticancer activity as compared with CNP or CDDP alone treatment, probably due to the synergistic antiproliferative and anti-inflammatory activities of CNP and CDDP.
Topics: Animals; Mice; Croton Oil; Natriuretic Peptide, C-Type; Croton; 9,10-Dimethyl-1,2-benzanthracene; Skin Neoplasms; Inflammation; Anti-Inflammatory Agents; Anthracenes; Body Weight
PubMed: 37352108
DOI: 10.1002/jbt.23423 -
Amino Acids Aug 2023Angiogenesis, invasion, and metastasis are the main events of cancer cells. JAK-1/STAT-3 is a key intracellular signaling transduction pathway, which controls the...
Angiogenesis, invasion, and metastasis are the main events of cancer cells. JAK-1/STAT-3 is a key intracellular signaling transduction pathway, which controls the growth, differentiation, apoptosis, invasion, and angiogenesis of various cancer cells. The present study explored the impact of allyl isothiocyanate (AITC) on the JAK-1/STAT-3 pathway in DMBA-induced rat mammary tumorigenesis. The mammary tumor was initiated through a single dose of 25 mg DMBA/rat by a subcutaneous injection administered near the mammary gland. We observed decreased body weight and increased the total number of tumors, tumor incidence, tumor volume, well-developed tumor, and histopathological abnormalities in DMBA-induced rats that were modulated after being treated with AITC. Staining of mammary tissues showed a high accumulation of collagen in DMBA-induced rats and it was normalized by the AITC treatment. Moreover, DMBA-induced mammary tissues showed up-regulated expressions of EGFR, pJAK-1, pSTAT-3, nuclear fraction of STAT-3, VEGF, VEGFR2, HIF-1α, MMP-2, and MMP-9 and the down-regulated expressions of cytosolic fraction of STAT-3 and TIMP-2. Oral administration of AITC on DMBA-induced rats inhibits angiogenesis and invasion by modifying these angiogenic and invasive markers. The finding of the present study was further confirmed by molecular docking analysis that shows a strong binding interaction between AITC with STAT-3 and cocrystal structure of STAT-3 glide energy of -18.123 and -72.246 (kcal/mole), respectively. Overall, the results suggested that AITC inhibits activation of the JAK-1/STAT-3 pathway, which subsequently prevents angiogenesis and invasion. It was recommended that AITC might develop a beneficial effect against breast cancer.
Topics: Rats; Animals; Molecular Docking Simulation; Signal Transduction; Neoplasms; ErbB Receptors; 9,10-Dimethyl-1,2-benzanthracene
PubMed: 37310534
DOI: 10.1007/s00726-023-03285-2 -
Life Sciences Aug 2023Breast cancer incidence keeps on growing and emerging as one of the major global challenges, therefore, the introduction of new approaches is of great demand. Drug...
AIMS
Breast cancer incidence keeps on growing and emerging as one of the major global challenges, therefore, the introduction of new approaches is of great demand. Drug repurposing is crucial to faster and cheaper discovery of anti-cancer drugs. The antiviral tenofovir disproxil fumarate (TF) was reported to decrease hepatocellular carcinoma risk by interfering with cell cycle and proliferation. This study aimed to scrutinize the role of TF alone or combined with doxorubicin (DOX) in 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast carcinoma rat model.
MATERIALS AND METHODS
Breast carcinoma was induced by DMBA (7.5 mg/kg, twice/week, subcutaneous into mammary gland) for 4 successive weeks. TF (25 and 50 mg/kg/day) was given orally and DOX (2 mg/kg) was injected once/week by tail vein starting from day 1.
KEY FINDINGS
The anti-cancerous effect of TF was mediated by suppression of oxidative stress markers and Notch signaling proteins (Notch1, JAG1, and HES1), attenuation of tumor proliferation markers (cyclin-D1 and Ki67), and boosting of apoptosis (P53 and Caspase3) and autophagy biomarkers (Beclin1 and LC3). In parallel, histopathological assessment displayed that mammary glands from animals treated with TF alone or combined with DOX showed better histopathological scores. Interestingly, TF and DOX co-treatment markedly decreased myocardial injury markers (AST, LDH, and CK-MB), restored the balance between GSH and ROS, prohibited lipid peroxidation, and preserved microscopic myocardial architecture.
SIGNIFICANCE
TF elicited antitumor activity via multiple molecular mechanisms. Moreover, combining TF with DOX might be a potential novel strategy to enhance DOX-anticancer activity and decrease its cardiac side effects.
Topics: Rats; Animals; Tenofovir; Doxorubicin; Apoptosis; Oxidative Stress; Biomarkers, Tumor; Carcinoma; 9,10-Dimethyl-1,2-benzanthracene
PubMed: 37236603
DOI: 10.1016/j.lfs.2023.121798 -
Naunyn-Schmiedeberg's Archives of... Nov 2023Oral cancer, a disfiguring and life threatening cancer, significantly affects the day-to-day life of not only the patients but also their family members in terms of life...
Ursolic acid-loaded chitosan nanoparticles suppress 7,12-dimethylbenz(a)anthracene-induced oral tumor formation through their antilipid peroxidative potential in golden Syrian hamsters.
Oral cancer, a disfiguring and life threatening cancer, significantly affects the day-to-day life of not only the patients but also their family members in terms of life quality and financial burden. India records higher incidence of oral cancer every year and is mainly due to the habituation of tobacco products and alcohol abuse. Delay in diagnosis and treatment influences India's higher incidence of oral cancer, where annually 50,000-60,000 oral carcinoma cases are reported. 7,12-dimethylbenz(a)anthracene (DMBA)-induced cancer in the oral cavity mimics human oral cancer in histopathological, molecular, and morphological aspects, and thus, by using this paradigm, the tumor inhibiting efficacy of medicinal plants or herbs and their components is scientifically validated. Ursolic acid, due to its multiple pharmacological effects, has been attracted, in recent years, for chemoprevention research program. Though, ursolic acid has been shown to have beneficial effects, its poor water solubility and bioavailability hinder to exert its 100% efficacy. Therefore, ursolic acid is encapsulated in either natural or synthetic polymers to enhance its therapeutic efficacy. Chitosan is one of the natural polymers that have been employed in the synthesis of nanoparticles to improve the drug efficacy. The present study has thus chosen ursolic acid-loaded chitosan nanoparticles (UACNP) to assess its anticancer efficacy in the DMBA-induced oral carcinoma. The anticancer efficacy of UACNP in experimental oral carcinogenesis was assessed by employing the status of oxidative markers and detoxification cascade as an end point. DMBA-induced abnormalities in the status of oxidative markers and detoxification cascade were reversed by ursolic acid-loaded chitosan nanoparticles. The tumor inhibiting or suppressing effect of UACNP is thus explored in experimental oral carcinogenesis.
Topics: Cricetinae; Animals; Humans; Mesocricetus; Chitosan; 9,10-Dimethyl-1,2-benzanthracene; Lipid Peroxidation; Mouth Neoplasms; Carcinogenesis; Nanoparticles; Carcinoma; Ursolic Acid
PubMed: 37162542
DOI: 10.1007/s00210-023-02509-2 -
Biotechnic & Histochemistry : Official... Nov 2023We evaluated the effects of prenatal and postnatal dietary zinc (Zn) deficiency or supplementation on mammary gland morphology and on acute response to...
We evaluated the effects of prenatal and postnatal dietary zinc (Zn) deficiency or supplementation on mammary gland morphology and on acute response to 7,12-dimethylbenzanthracene (DMBA) in pubertal female rats. On gestational day 10 (GD 10), rat dams were allocated randomly into three experimental groups of 10: a Zn-adequate diet group (ZnA) fed 35 mg Zn/kg chow, a Zn-deficient diet group (ZnD) fed 3 mg ZN/kg chow and a Zn-supplemented diet group (ZnS) fed 180 mg Zn/kg chow. After weaning, female offspring were fed the same diet as their dams until postnatal day 53 (PND 53). All animals received a single 50 mg/kg dose of DMBA on PND 51 and were euthanized on PND 53. Female ZnD offspring exhibited significantly less weight gain compared to the ZnA group and reduced mammary gland development compared to the ZnD and ZnA groups. By PND 53, the Ki-67 labeling index in mammary gland epithelial cells was significantly greater for the ZnS group than for the ZnA and ZnD groups. Apoptosis and ER-α indices did not differ among groups. The ZnD group exhibited significantly increased lipid hydroperoxide (LOOH) levels and decreased catalase and glutathione peroxidase (GSH-Px) activity compared to the ZnA and ZnS groups. The ZnS group exhibited significantly reduced superoxide dismutase (SOD) activity compared to the ZnA and ZnS groups. We observed atypical ductal hyperplasia in the mammary gland of female ZnS group offspring compared to the ZnA and ZnD groups and decreased expression of the and genes related to apoptosis inhibition and DNA damage repair, respectively. Both the Zn-deficient and Zn-supplemented diet exerted adverse effects on offspring mammary gland morphology and acute response to DMBA.
Topics: Pregnancy; Rats; Female; Animals; 9,10-Dimethyl-1,2-benzanthracene; Diet; Apoptosis; Zinc
PubMed: 37022146
DOI: 10.1080/10520295.2023.2196092 -
Journal of Ethnopharmacology Jul 2023Despite various prevention and treatment measures, the incidence and mortality due to breast cancer has been increasing globally. Passiflora edulis Sims is a plant used...
ETHNOPHARMACOLOGICAL RELEVANCE
Despite various prevention and treatment measures, the incidence and mortality due to breast cancer has been increasing globally. Passiflora edulis Sims is a plant used for the treatment of various diseases in traditional medicine, including cancers.
AIM OF THE STUDY
To assess the anti-breast cancer activity of the ethanolic extract of P. edulis leaves in vitro and in vivo.
MATERIAL AND METHODS
In vitro, the cell growth and proliferation were determined based on the MTT and BrdU assays. The flow cytometry was used to analyze the cell death mechanism while, cell migration, cell adhesion and chemotaxis were assayed for anti-metastatic potential. In vivo, 56 female Wistar rats aged 45-50 days (∼75 g) were exposed to 7,12-dimethylbenz(a)anthracene-DMBA except the normal group. Negative control group (DMBA) received solvent dilution throughout the study; standards groups (tamoxifen - 3.3 mg/kg BW and letrozole - 1 mg/kg BW) as well as P. edulis leaves ethanolic extract groups (50, 100 and 200 mg/kg) treated for 20 weeks. Tumor incidence, tumor burden and volume, CA 15-3 serum' level, antioxidant, inflammatory status and histopathology were assessed.
RESULTS
P. edulis extract showed a significant and concentration-dependent inhibition of MCF-7 and MDA-MB 231 cells growth at 100 μg/mL. It inhibited cell proliferation and clones' formation and induced apoptosis in MDA-MB 231 cells. The migration of cell into the zone freed of cells and the number of invading cells after the 48 and 72 h were significantly diminished while, it increased their adherence to collagen and fibronectin extracellular matrix as does Doxorubicin. In vivo, all rats in the DMBA group exhibited a significant (p < 0.001) increase in tumor volume, tumor burden and grade (adenocarcinoma of SBR III) and pro-inflammatory cytokine levels (TNF-α, INF-γ, IL-6 and IL-12). P. edulis extract at all tested doses significantly inhibited the DMBA-induced increase in tumor incidence, tumor burden and grade (SBR I) as well as pro-inflammatory cytokines. Moreover, it increased enzymatic and non-enzymatic antioxidants (SOD, catalase, and GSH) and decreased MDA levels although a greater effect was observed with Tamoxifen and Letrozole. P. edulis has medium content on polyphenols, flavonoids and tannins.
CONCLUSION
P. edulis has chemo-preventive effects against DMBA-induced breast cancer in rats probably through its antioxidative, anti-inflammatory and apoptosis-inducing potentials.
Topics: Rats; Animals; Rats, Wistar; Passiflora; 9,10-Dimethyl-1,2-benzanthracene; Passifloraceae; Letrozole; Anticarcinogenic Agents; Plant Extracts; Antioxidants; Tamoxifen; Ethanol; Carcinoma
PubMed: 36966851
DOI: 10.1016/j.jep.2023.116408