RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: In Brazil, latex of Himatanthus drasticus is used to treat inflammation, wound healing and cancer. The present study evaluated the antitumoral potential of H. drasticus latex (HdCL) in Sarcoma 180-bearing mice (S180). MATERIALS AND METHODS: HdCL was obtained in Crato-CE, Brazil. Qualitative phytochemicals assays, nuclear magnetic resonance (NMR) and microbiological analyzes were performed. Swiss mice were divided into six groups, according to tumor forms: 1) ascitic model, GI (Control; 0.9% saline), GII (S180asc) and GIII (S180asc/HdCL/14 days); 2) solid model, GIV (Control; 0.9% saline), GV (S180sol) and GVI (S180sol/HdCL/10 days). HdCL and 0.9% saline were administered at 0.2â¯mL, SID, by gavage, for 10 or 14 days. For ascitic model, 0.5â¯mL of S180 suspension (4×106 cells/mL) was inoculated intraperitoneally and for solid model, cells were inoculated subcutaneously (25⯵L) on the right hind paw of mice. Blood samples were collected for hematological and oxidative stress evaluation. Thickness, volume and weight of paws were measured in solid model. After euthanasia, spleen, liver and kidney were collected in order to assess the relative organ weight. Tissue fragments of paws and popliteal lymph nodes (PLN) were analyzed by H&E and CD4+, CD8+, HSP-60+ and Foxp3+ immunohistochemistry. RESULTS: HdCL presented milky aspect and pinkish supernatant. Phenols, flavonols, flavanones, free steroids and cinnamoyl derivatives of lupeol, α-amyrin and ß-amyrin were detected at the phytochemistry analysis. HdCL did not alter the relative weight of organs, hematological parameters and volume of ascitic fluid recovered. In solid model, HdCL reduced (Pâ¯<â¯0.05) paw volume, but did not altered thickness, paw weight and histological parameters. S180sol induced necrosis, metastasis and destruction of bone, cartilage and muscles. Bleeding, vessel congestion and oncocytes were observed in PLN. In paw, HdCL did not alter FoxP3+ and HSP-60+ expressions but reduced the CD4+ and CD8+ expressions, while at PLN, HdCL reduced the expressions of all markers. HdCL decreased (Pâ¯<â¯0.05) serum levels of malondialdehyde in ascitic model. CONCLUSIONS: Treatment with HdCL reduced oxidative damage and modulated the expressions of CD4+, CD8+, FoxP3+and HSP-60+ in S180 solid tumor model, which can be associated to the presence of triterpenes, such as α-amyrin, ß-amyrin and lupeol cinnamate. Present data emphasizes the importance of immune system in cancer and highlights the evaluation of the pharmacological properties of plants used by population as phytoterapics.
Asunto(s)
Apocynaceae/química , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Sarcoma 180/tratamiento farmacológico , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Brasil , Antígenos CD4/genética , Antígenos CD8/genética , Chaperonina 60/genética , Femenino , Factores de Transcripción Forkhead/genética , Malondialdehído/sangre , Ratones , Proteínas Mitocondriales/genética , Sarcoma 180/inmunología , Sarcoma 180/patologíaRESUMEN
Camundongos infectados com 60 cercárias de Schistosoma mansoni tornaram-se mais resistentes ao sarcoma 180 na forma de tumor ascítico. A inoculaçäo das células tumorais foi feita no 50§ dia de infecçäo e a evoluçäo do tumor foi acompanhada através da pesagem dos animais com intervalos de 48 horas. Nos camundongos infectados o ganho de peso (formaçäo da ascite) começou mais tarde e foi menor do que nos controles näo infectados. Também o número de células tumorais na cavidade peritoneal 72 horas após a implantaçäo do tumor foi menor no grupo infectado. Este aumento de resistência a um tumor transplantável possivelmente está relacionado ao efeito de endotoxinas sobre a atividade de tumoricida dos macrofagos ativados pela infecçäo. A imunossupressäo induzida pela infecçäo favorece a proliferaçäo de bactéria da flora endógena aumentando a quantidade de endotoxinas absorvidas pelo intestino
Asunto(s)
Ratas , Animales , Terapia de Inmunosupresión , Sarcoma 180/inmunología , Esquistosomiasis mansoni/inmunologíaRESUMEN
An evaluation was made on the growth of Sarcoma 180 (S 180) in normal and splenectomized BALB/c mice which had been immunized 40 days before the tumor challenge with BCG, either intradermally or in diffusion chambers placed in the peritoneal cavity. Immunization with intradermal BCG did not modify the growth of subcutaneous S 180, whereas it provided significant protection when the tumor was inoculated with BCG. Previous treatment with BCG in diffusion chambers had no effect on the development of S 180, but significantly decreased the percentage of survival of mice inoculated with S 180 mixed with BCG, as compared to the homologous group immunized with intradermal BCG. Splenectomy performed before the challenge with S 180, enabled 56% of mice lacking previous immunization to survive and increased this percentage to 100% when the tumor was inoculated mixed with BCG. As for splenectomized mice immunized with BCG within diffusion chambers and challenged with S 180, there was 90% of survival and 69% in those challenged with S 180 mixed with BCG. These results would suggest that the action of BCG on the growth of S 180 differs according to whether the mycobacteria are in direct contact with the host or exert their effect by means of soluble antigens capable of passing through the millipore filter of the diffusion chambers. These effects would be conditioned by the immunological state of the host.