RESUMO
This work describes a pharmacological screening of Brazilian medicinal plants through their anti-inflammatory and cytotoxicity activities. Cytotoxicity activity of Mouriri elliptica and Alchornea glandulosa as well as the drugs celecoxib and doxorubicin were evaluated in cultures of peritoneal macrophages. The immune system influence of these samples was analyzed by determining production/inhibition of NO, production of tumor necrosis factor-α and production of interleukin-10. Regarding the production/inhibition of NO, there was NO production by M. elliptica and NO inhibition when the cells were exposed to A. glandulosa; Macrophages generally produce more NO, plus TNF-α and less IL-10, when associated to the tumor phenomenon, characterizing the inflammation involved in cancer. A. glandulosa showed anti-inflammatory effect, inhibited NO production and it was associated with low TNF-α production, although not as low as the macrophages associated with celecoxib and doxorubicin. These cytokines were not different in animals with tumor. Celecoxib confirms its anti-inflammatory action by markedly inhibiting NO and TNF-α, but also inhibiting IL-10 which is an anti-inflammatory cytokine. Doxorubicin inhibited NO in a higher percentage in the group of animals with tumor, although the literature reports that this drug stimulates the production of NO and this collaborates with its cytotoxic effect.
Assuntos
Antineoplásicos , Carcinoma , Plantas Medicinais , Animais , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Citocinas , Ecossistema , Óxido Nítrico , Fator de Necrose Tumoral alfaRESUMO
Integrin αvß3 is most likely the foremost modulator of angiogenesis among all known integrins. Recombinant disintegrin DisBa-01, originally obtained from snake venom glands, binds to αvß3, thereby significantly inhibiting adhesion and generating in vivo anti-metastatic ability. However, its function in mediator production is not clear. Here, we observed that the mediators VEGF-A, IL-8, and TGF-ß are not produced by human umbilical vein endothelial cells (HUVEC cell line) or monocyte/macrophage cells (SC cell line) when cells adhered to vitronectin. However, when exposed to DisBa-01, HUVECs produced higher levels of TGF-ß, and SC cells produced higher levels of VEGF-A. Nonetheless, HUVECs also showed an enhancement of apoptosis after losing adherence when exposed to disintegrin, which is a characteristic of anoikis. We propose that disintegrin DisBa-01 could be used to modulate integrin αvß3 functions.
Assuntos
Inibidores da Angiogênese/farmacologia , Citocinas/biossíntese , Desintegrinas/farmacologia , Integrina alfaVbeta3/metabolismo , Apoptose/efeitos dos fármacos , Adesão Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ensaios de Seleção de Medicamentos Antitumorais , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Proteínas Recombinantes/farmacologia , Vitronectina/metabolismoRESUMO
Palladium(II) complexes are an important class of cyclopalladated compounds that play a pivotal role in various pharmaceutical applications. Here, we investigated the antitumour, anti-inflammatory, and mutagenic effects of two complexes: [Pd(dmba)(Cl)tu] (1) and [Pd(dmba)(N3)tu] (2) (dmba = N,N-dimethylbenzylamine and tu = thiourea), on Ehrlich ascites tumour (EAT) cells and peritoneal exudate cells (PECs) from mice bearing solid Ehrlich tumour. The cytotoxic effects of the complexes on EAT cells and PECs were assessed using the 3-(4,5-dimethylthiazol-3-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The effects of the complexes on the immune system were assessed based on the production of nitric oxide (NO) (Griess assay) and tumour necrosis factor-alpha (TNF-alpha), interleukin-12 (IL-12), and interleukin-10 (IL-10) (ELISA). Finally the mutagenic activity was assessed by the Ames test using the Salmonella typhimurium strain TA 98. Cisplatin was used as a standard. The IC50 ranges for the growth inhibition of EAT cells and PECs were found to be (72.8 +/- 3.23) microM and (137.65 +/- 0.22) microM for 1 and (39.7 +/- 0.30) microM and (146.51 +/- 2.67) microM for 2, respectively. The production of NO, IL-12, and TNF-alpha, but not IL-10, was induced by both complexes and cisplatin. The complexes showed no mutagenicity in vitro, unlike cisplatin, which was mutagenic in the strain. These results indicate that the complexes are not mutagenic and have potential immunological and antitumour activities. These properties make them promising alternatives to cisplatin.