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Mediators Inflamm
2017 Jan 01;2017:6898505. doi: 10.1155/2017/6898505.
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Morita-Baylis-Hillman Adducts Display Anti-Inflammatory Effects by Modulating Inflammatory Mediator Expression in RAW264.7 Cells.
Faheina-Martins GV
,
Leite JA
,
Dantas BB
,
Lima-Júnior CG
,
Vasconcellos MLAA
,
Rodrigues-Mascarenhas S
,
Araújo DAM
.
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Inflammatory response plays an important role not only in the normal physiology but also in pathologies such as cancers. The Morita-Baylis-Hillman adducts (MBHA) are a novel group of synthetic molecules that have demonstrated many biological activities against some parasitic cells such as Plasmodium falciparum, Leishmania amazonensis, and Leishmania chagasi, and antimitotic activity against sea urchin embryonic cells was also related. However, little is known about the mechanisms induced by MBHA in inflammatory process and its relation with anticancer activity. The present work investigated the cytotoxicity of three MBHA derivatives (A2CN, A3CN, and A4CN), on human colorectal adenocarcinoma, HT-29 cells, and their anti-inflammatory activities were examined in lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophage cells, being these derivatives potentially cytotoxic to HT-29 cells. Coincubation with A2CN, A3CN, or A4CN and LPS in RAW264.7 cells inhibited NO production, as well as the production of reactive oxygen species (ROS) was also repressed. The mRNA expressions of IL-1β and IL-6 were significantly downregulated by such MBHA compounds in RAW264.7 cells, but only A2CN was able to inhibit the COX-2 gene expression. We also showed that MBHA compounds decreased almost to zero the production of IL-1β and IL-6. These findings display that such MBHA compounds exhibit anticancer and anti-inflammatory activities.
Figure 2. Cell viability of RAW264.7 cells incubated for 22 h with MBHA (A2CN, A3CN, or A4CN). Data were obtained by MTT assay. Cells were treated for 22 h. CTR, cells without LPS and MBHA compounds. LPS, cells incubated with LPS (1 μg/mL). MBHA (μM) means cells cultured with A2CN, A3CN, or A4CN as indicated. Results are mean ± SEM of three independent experiments of percentage of cell viability performed in triplicate and were analyzed by ANOVA followed by Newman-Keuls post hoc test.
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