Integrin αvβ3 is most likely the foremost modulator of angiogenesis among all known integrins. Recombinant disintegrin DisBa-01, originally obtained from snake venom glands, binds to αvβ3, 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-β 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-β, 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 αvβ3 functions.
This work describes a pharmacological screening of Brazilian medicinal plants through their anti-infl ammatory 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 infl uence 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 infl ammation involved in cancer. A. glandulosa showed anti-infl ammatory 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 confi rms its anti-infl ammatory action by markedly inhibiting NO and TNF-α, but also inhibiting IL-10 which is an anti-infl ammatory 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.
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-infl ammatory, and mutagenic effects of two complexes: [Pd(dmba)(Cl)tu] (1) and [Pd(dmba)(N 3 )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-α (TNF-α), 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 IC 50 ranges for the growth inhibition of EAT cells and PECs were found to be (72.8 ± 3.23) μM and (137.65 ± 0.22) μM for 1 and (39.7 ± 0.30) μM and (146.51 ± 2.67) μM for 2, respectively. The production of NO, IL-12, and TNF-α, 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.
BackgroundRibosome-inactivating proteins (RIP) have been studied in the search for toxins that could be used as immunotoxins for cancer treatment. Pulchellin, a type 2 RIP, is suggested to induce immune responses that have a role in controlling cancer.MethodsThe percentage of dendritic cells and CD4+ and CD8+ T cells in the spleen (flow cytometry), cytokines’ release by PECs and splenocytes (ELISA) and nitric oxide production by PECs (Griess assay) were determined from tumor-bearing mice injected intratumorally with 0.1 ml of pulchellin at 0.75 μg/kg of body weight. Statistical analysis was performed by one-way ANOVA with Tukey’s post hoc test.ResultsPulchellin-treated mice showed significant immune system activation, characterized by increased release of IFN-γ and Th2 cytokines (IL-4 and IL-10), while IL-6 and TGF-β levels were decreased. There was also an increase in macrophage’s activation, as denoted by the higher percentage of macrophages expressing adhesion and costimulatory molecules (CD54 and CD80, respectively).ConclusionsOur results suggest that pulchellin is promising as an adjuvant in breast cancer treatment.
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.
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