RESUMEN
Melanoma is a highly metastatic and rapidly progressing cancer, a leading cause of mortality among skin cancers. The melanoma microenvironment, formed from the activity of malignant cells on the extracellular matrix and the recruitment of immune cells, plays an active role in the development of drug resistance and tumor recurrence, which are clinical challenges in cancer treatment. These tumoral metabolic processes are affected by proteins, including Galectin-3 (Gal-3), which is extensively involved in cancer development. Previously, we characterized a partially methylated mannogalactan (MG-Pe) with antimelanoma activities. In vivo models of melanoma were used to observe MG-Pe effects in survival, spontaneous, and experimental metastases and in tissue oxidative stress. Analytical assays for the molecular interaction of MG-Pe and Gal-3 were performed using a quartz crystal microbalance, atomic force microscopy, and contact angle tensiometer. MG-Pe exhibits an additive effect when administered together with the chemotherapeutic agent dacarbazine, leading to increased survival of treated mice, metastases reduction, and the modulation of oxidative stress. MG-Pe binds to galectin-3. Furthermore, MG-Pe antitumor effects were substantially reduced in Gal-3/KO mice. Our results showed that the novel Gal-3 ligand, MG-Pe, has both antitumor and antimetastatic effects, alone or in combination with chemotherapy.
Asunto(s)
Antineoplásicos , Galectina 3 , Melanoma , Neoplasias Cutáneas , Animales , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Dacarbazina/metabolismo , Dacarbazina/farmacología , Dacarbazina/uso terapéutico , Galectina 3/metabolismo , Galectina 3/farmacología , Galectina 3/uso terapéutico , Ligandos , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Ratones , Recurrencia Local de Neoplasia , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/metabolismo , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/fisiologíaRESUMEN
Abstract Tropaeolum majus L., Tropaeolaceae, popularly known in Brazil as 'capuchinha' is widely used due its anti-inflammatory, antiseptic, anti-hypertensive and anti-depressive properties. However, scientific investigations about its effects on the central nervous system are still scarce. This study investigated the central pharmacological actions of the prolonged treatment with a hydroethanolic extract of T. majus in male Wistar rats in the elevated plus maze and hole-board behavioral models. For this, rats were daily treated with distillated water (negative control); diazepam (1 mg/kg) or hydroethanolic extract of T. majus (75, 150 and 300 mg/kg), for 29 days (by gavage) and were submitted to elevated plus maze and hole-board. Animals treated with all hydroethanolic extract of T. majus or diazepam doses increased the percentage of entries in open arms when compared to control group. However, only treatment with diazepam increased the length of time spent in the open arms of the elevated plus maze. No differences between all groups were observed regardless rearing, grooming, stretched-attend postures and defecation rates. In the HB test, in opposite to diazepam, treatment with hydroethanolic extract of T. majus did not interfere in the exploratory activity of rats. The hydroethanolic extract of T. majus promotes anxiolytic-like effects when orally administered in rats.
RESUMEN
Abstract Casearia sylvestris Sw., Salicaceae, is an important medicinal plant widely used in Brazil for the treatment of various cardiovascular disorders. This species was included as of interest by Brazilian Unified Health System. Although preclinical studies described cardiovascular protective effects and apparent absence of toxicity, no studies have evaluated its carcinogenic potential. In this study, we proposed a short-term carcinogenesis evaluation of C. sylvestris in Wistar rats, aiming to check the safety of this species to use it as proposed by Brazilian Unified Health System. C. sylvestris leaves were obtained and the crude extract was prepared by maceration from methanol/water. Wistar rats were orally treated for 12 weeks with 50, 250 or 500 mg kg−1 of crude extract or vehicle. Body weight, daily morbidity and mortality were monitored. Blood and bone marrow samples were collect for micronucleus test, comet assay and tumor markers evaluation. Vital organs were removed to macro and histopathological analyses. The crude extract did not induce mutagenic and genotoxic effects and no alterations were observed in important tumor markers. Finally, no detectable signs of injury through gross pathology or histopathological examinations were observed. Our results certify the absence of the crude extract toxicity, indicating its safety, even at prolonged exposure as proposed by Brazilian Unified Health System.