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Purpose: Abnormal acetylation modification is a common epigenetic change in tumorigenesis and is closely related to the progression of colorectal cancer (CRC). Our previous studies have suggested that black raspberry (BRB) anthocyanins have a significant chemopreventive effect against CRC. This study investigated whether protein acetylation plays an important role in BRB anthocyanins-mediated regulation of CRC progression. Methods: We used the AOM-induced CRC mouse model and the CRC cell lines SW480 and Caco-2 to explore the potential role of acetylation of histone H4 and NF-κB signaling pathway-related proteins (non-histone proteins) in the antitumor process mediated by BRB anthocyanins. The expression of related proteins was detected by western blot. ROS level was detected by immunofluorescence. Results: BRB anthocyanins affected the acetylation level by down-regulating the expression of Sirtuin1 (SIRT1) and up-regulating the expression of MOF and EP300. The acetylation level of lysine sites on histone H4 (H4K5, H4K12 and H4K16) was increased. Furthermore, following BRB anthocyanins treatment, the expression of ac-p65 was significantly up-regulated and the NF-κB signal pathway was activated, which in turn up-regulated Bax expression and inhibited Bcl-2, cyclin-D1, c-myc and NLRP3 expression to promote CRC cell cycle arrest, apoptosis and relieve inflammation. Conclusion: The findings suggested that protein acetylation could play a critical role in BRB anthocyanins-regulated CRC development. [ABSTRACT FROM AUTHOR]

Epithelial Mesenchymal Transition (EMT) plays a major role in cancer metastasis. Several genes have been shown to play a role in EMT, and one of these is Amplified-in-breast cancer 1 (AIB1), which has oncogenic function and is known to be amplified in breast cancer. However, the role of AIB1 in EMT remains largely undefined at the molecular level. In this study, the effect of AIB1 overexpression on the EMT of the breast cancer cell line T47D was investigated. Overexpression of AIB1 disrupted the epithelial morphology of the cells. At the same time, the cells displayed a strong metastasis and reduced level of the epithelial marker E-cadherin. In contrast, knockdown of AIB1 in T47D cells increased cell-cell adhesion and produced weak metastasis, as well as a higher level of E-cadherin expression. We proposed that the regulation of EMT by AIB1 occurred through the action of the transcription factor SNAI1, and demonstrated that such interaction required the participation of ERα and the presence of ERα-binding site on SNAI1 promoter. The expression level of E-cadherin and the extent of cell migration and invasion in SNAI1-knocked down T47D cells that overexpressed AIB1 were similar to those of T47D cells that did not overexpress AIB1 and had no SNAI1 knockdown. Taken together, these results suggested that AIB1 exerted its effect on EMT through its interaction with ERα, which could directly bind to the ERα-binding site on the SNAI1 promoter, allowing the AIB1-ERα complex to promote the transcription of SNAI1 and eventually led to repression of E-cadherin expression, consistent with the loss of E-cadherin being a hallmark of EMT. [ABSTRACT FROM AUTHOR]

[Display omitted] • NSAID selenocyanate derivatives were found to exhibit a neuroprotective effect. • 1-39 and 1A-38 could significantly suppress NOX2 expression and ROS production. • There appeared to be a link between the NLRP3 signaling pathway and the neuroprotective effect of 1-39 and 1A-38. • NSAID selenocyanate derivatives might be considered as potential therapeutic agents of neurodegenerative diseases. Neuro-inflammation is an immune response of the central nervous system (CNS) to pathogens, and it is associated with a variety of neurodegenerative diseases. Microglial cells are the main category of macrophages in the CNS parenchyma, and they represent one of the most important cellular drivers and regulators of neuroinflammation. In this study, nine new organoselenium compounds based on the hybridization of nonsteroidal anti-inflammatory drugs (NSAIDs) skeleton and organoselenium motif (-SeCN and -SeCF3) were synthesized and their potential anti-neuroinflammatory effects were evaluated using LPS-induced BV2 mouse microglia. The cells were first treated with the organoselenium compounds and the extent of oxidative stress and inflammatory response of the cells was determined by measuring the levels of NO, ROS, IL-1β, and IL-18. Among the nine compounds, 1-39 and 1A-38 exhibited the most significant effect on oxidative stress and inflammatory response. Subsequent studies carried out with 1-39 and 1A-38 showed that both compounds could reduce the production of ROS in the cells, probably through down-regulating NOX2 and its downstream targets, including TXNIP (thioredoxin-interacting protein) and NLRP3 (NOD-like receptor protein 3). In addition, 1-39 and 1A-38 also suppressed the ability of the cells to secret IL-18 and IL-1β, which greatly dampened the response of the cells to LPS-induced inflammation. Our finding demonstrated that organoselenium compounds derived from NSAID might play an important role in the protection of brain microglia against inflammation-related neurodegenerative disease by potentially down-regulating the NOX2/NLRP3 signaling axis. [ABSTRACT FROM AUTHOR]