Six new monoterpenoid indole alkaloids, kopsinidines C-E (1-3), 11,12-methylenedioxychanofruticosinic acid (4), 12-methoxychanofruticosinic acid (5), and N(4)-methylkopsininate (7), as well as chanofruticosinic acid (6, as a natural product) and 23 known alkaloids, were obtained from the twigs and leaves of Kopsia officinalis. Their structures were characterized by physical data analysis. All isolated compounds were evaluated for their immunosuppressive activity on human T cell proliferation. Rhazinilam (29) significantly inhibited human T cell proliferation activated by anti-CD3/anti-CD28 antibodies (IC = 1.0 μM) and alloantigen stimulation (IC = 1.1 μM) without obvious cytotoxicity for naïve human T cells and peripheral blood mononuclear cells (0-320 μM). Although it did not affect T cell activation, it induced T cell cycle arrest in the G/M phase and inhibited proinflammatory cytokine production in activated T cells.

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The present study aimed to evaluate whether bromodomain 4 (BRD4) is expressed in Cal27 cells and to assess the effect of JQ1 on cell proliferation, apoptosis, invasion and BRD4, C-Myc and Twist expression in Cal27 cells. Immunofluorescence staining was used to determine whether BRD4 was expressed in Cal27 cells. Cell viability and proliferation were evaluated using CCK-8 assay. Flow cytometry was used to determine the apoptosis and cell cycle distribution. The cell invasion was evaluated using Transwell plate. The expression levels of BRD4, C-Myc and Twist were determined by quantitative RT-PCR (qRT-PCR) and western blotting. BRD4 was highly expressed in Cal27 cells. JQ1 inhibited cell proliferation, induced cell apoptosis, induced cell cycle arrest, and inhibited cell invasion. Gene and protein expression levels of BRD4, C-Myc and Twist were downregulated in cells treated with JQ1. JQ1 inhibited Cal27 cell growth and invasion, and downregulated expression of several oncogenes. JQ1 may be a new drug for oral squamous cell carcinoma treatment.

BackgroundBromodomain-containing protein 4 (BRD4) inhibition is a new therapeutic strategy for many malignancies. In this study, we aimed to explore the effect of BRD4 inhibition by JQ1 on in vitro cell growth, migration and invasion of salivary adenoid cystic carcinoma (SACC).MethodsThe human normal epithelial cells and SACC cells (ACC-LM and ACC-83) were treated with JQ1 at concentrations of 0, 0.1, 0.5 or 1 μM. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Cell apoptosis and cell cycle distribution was evaluated by Flow cytometry. Immunofluorescence staining was used to examine the expression of BRD4 in SACC cells. The quantitative real-time polymerase chain reaction (qRT-PCR) assay and western blot assay were performed to examine messenger RNA (mRNA) and protein levels in SACC cells. Wound-healing assay and transwell assay were used to evaluate the activities of migration and invasion of SACC cells.ResultsJQ1 exhibits no adverse effects on proliferation, cell cycle and cell apoptosis of the normal human epithelial cells, while suppressed proliferation and cell cycle, and induced apoptosis of SACC cells, down-regulated the mRNA and protein levels of BRD4 in SACC cells, meanwhile reduced protein expressions of c-myc and BCL-2, two known target genes of BRD4. Moreover, JQ1 inhibited SACC cell migration and invasion by regulating key epithelial–mesenchymal transition (EMT) characteristics including E-cadherin, Vimentin and Twist.ConclusionsBRD4 is an important transcription factor in SACC and BRD4 inhibition by JQ1 may be a new strategy for SACC treatment.

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