ABSTRACT
Prostate cancer (PCa) is one of the most common cancers in men, with a huge impact on their health. The use of Castanea sativa Mill. flowers (CFs) in beverages has been reported, through ancestral claims, as having health benefits. In vitro research has evidenced the properties of CFs, such as antitumor and antioxidant activities. This study aimed to evaluate the effects of CF extract in an animal model of PCa. Forty male Wistar Unilever rats were randomly assigned to four groups: control, induced, control + CF, and induced + CF groups. Animals from the induced groups were exposed to a multistep protocol for PCa induction. The CF extract, rich in trigalloyl-HHDP-glucoside and obtained via decoction, was administered to the CF groups in drinking water (3 mg per animal per day) for 49 weeks. Animals were sacrificed at 61 weeks of age. Regarding the effects of CFs on dorsolateral prostate tumorigenesis, no significant differences were observed between the induced and induced + CF groups. However, animals exposed to the CF extract showed fewer inflammation areas on the dorsolateral prostate lobe than those not exposed to CF. Moreover, the CF extract alleviated the hepatic oxidative stress associated with the multistep protocol, resulting in lower levels of lipid peroxidation. These results suggest that CF extract has antioxidant and anti-inflammatory properties.
Subject(s)
Antineoplastic Agents/pharmacology , Fagaceae/chemistry , Flowers/chemistry , Plant Extracts/pharmacology , Prostatic Neoplasms/metabolism , Animals , Liver/drug effects , Liver/metabolism , Male , Neoplasms, Experimental , Oxidative Stress/drug effects , Prostate/drug effects , Prostate/metabolism , Prostate/pathology , Prostatic Neoplasms/pathology , Rats , Rats, WistarABSTRACT
AIM: Exercise training has been suggested as a non-pharmacological approach to prevent skeletal muscle wasting and improve muscle function in cancer cachexia. However, little is known about the molecular mechanisms underlying such beneficial effect. In this study, we aimed to, firstly, examine the contribution of TWEAK signalling to cancer-induced skeletal muscle wasting and, secondly, evaluate whether long-term exercise alters TWEAK signalling and prevents muscle wasting. METHODS: Female Sprague-Dawley rats were randomly assigned to control and exercise groups. Fifteen animals from each group were exposed to N-Methyl-N-nitrosourea carcinogen. Animals in exercise groups were submitted to moderate treadmill exercise for 35 weeks. After the experimental period, animals were killed and gastrocnemius muscles were harvested for morphological and biochemical analysis. RESULTS: We verified that exercise training prevented tumour-induced TWEAK/NF-κB signalling in skeletal muscle with a beneficial impact in fibre cross-sectional area and metabolism. Indeed, 35 weeks of exercise training promoted the upregulation of PGC-1α and oxidative phosphorylation complexes. This exercise-induced muscle remodelling in tumour-bearing animals was associated with less malignant mammary lesions. CONCLUSION: Data support the benefits of an active lifestyle for the prevention of muscle wasting secondary to breast cancer, highlighting TWEAK/NF- κB signalling as a potential therapeutic target for the preservation of muscle mass.
Subject(s)
Apoptosis Regulatory Proteins/biosynthesis , Cachexia/metabolism , Mammary Neoplasms, Experimental/complications , Membrane Proteins/biosynthesis , Physical Conditioning, Animal/methods , Signal Transduction , Tumor Necrosis Factors/biosynthesis , Animals , Cachexia/etiology , Cytokine TWEAK , Disease Models, Animal , Female , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscular Atrophy/etiology , Muscular Atrophy/metabolism , NF-kappa B/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Signal Transduction/physiologyABSTRACT
BACKGROUND: Breast cancer remains a leading cause of death by cancer worldwide. It is commonly accepted that angiogenesis and the expression of angiogenic factors such as vascular endothelial growth factor-A (VEGF-A) is associated with the increased risk of metastasis and poor patient outcome. OBJECTIVE: This work aimed to evaluate the effects of long-term exercise training on the growth and vascularization of mammary tumors in a rat model. MATERIALS AND METHODS: Fifty female Sprague-Dawley rats were divided into four groups: two N-methyl-N-nitrosourea (MNU)-exposed groups (exercised and sedentary) and two control groups (exercised and sedentary). MNU was administered once, intraperitoneally at 7 weeks-old. Animals were then exercised on a treadmill for 35 weeks. Mammary tumors were evaluated using thermography, ultrasonography [Power Doppler (PDI), B Flow and contrast-enhanced ultrasound (CEUS)], and immunohistochemistry (VEGF-A). RESULTS: Both, MNU sedentary and exercised groups showed 100% of tumor incidence, but exercised animals showed less tumors with an increased latency period. Exercise training also enhanced VEGF-A immunoexpression and vascularization (microvessel density, MVD) (p<0.05), and reduced histological aggressiveness. Ultrasound and thermal imaging analysis confirmed the enhanced vascularization of tumors on exercised animals. CONCLUSION: Long-term exercise training increased VEGF-A expression, leading to enhanced tumor vascularization and reduced tumor burden, multiplicity and histological aggressiveness.
Subject(s)
Mammary Neoplasms, Experimental/blood supply , Mammary Neoplasms, Experimental/physiopathology , Neovascularization, Pathologic/physiopathology , Physical Conditioning, Animal , Animals , Female , Immunohistochemistry , Mammary Neoplasms, Experimental/diagnostic imaging , Mammary Neoplasms, Experimental/pathology , Organ Size , Rats, Sprague-Dawley , Thermography , Time Factors , Ultrasonography , Vascular Endothelial Growth Factor A/metabolismABSTRACT
BACKGROUND: As the worldwide breast cancer burden increases, non-invasive tools, such as ultrasonography and thermography are being increasingly sought after. N-methyl-N-nitrosourea-induced rat mammary tumors are important tools to investigate the usefulness of such imaging techniques. OBJECTIVE: This study aimed to integrate both ultrasonographic and thermographic approaches to the vascularization and the superficial temperature of chemically-induced rat mammary tumors. MATERIALS AND METHODS: Twenty-five female Sprague-Dawley rats were divided into two groups: group I (intraperitoneally administered with N-methyl-N-nitrosourea) and group II (control group). Thirty-five weeks after the administration of the carcinogen, mammary tumors were evaluated using Power Doppler, B Flow and Contrast-enhanced ultrasound, thermography and histology analyses. RESULTS: Group I animals showed an average of 2.5 mammary tumors per animal, mostly papillary and cribriform non-invasive carcinomas. B Flow detected higher counts of colour pixels than Power Doppler. Contrast-enhanced ultrasound analysis showed a centripetal enhancement order of contrast agent and clear margins. Maximum tumor temperature and thermal amplitude determined by thermography were significantly correlated with tumor volume and with color pixel density, determined by Power Doppler. CONCLUSION: B Flow was more sensitive than Power Doppler in detecting tumor vessels, but Power Doppler correlates with thermographic data concerning superficial temperature and may reflect tumor angiogenesis.
