Kusunokinin, a lignan compound, inhibits cancer cell proliferation and induces apoptosis; however, the role of kusunokinin is not fully understood. Here, we aimed to identify a target protein of (-)-kusunokinin and determine the protein levels of its downstream molecules. We found that (-)-kusunokinin bound 5 possible target proteins, including CSF1R, MMP-12, HSP90-α, CyclinB1 and MEK1 with ΔG_bind less than -10.40 kcal/mol. MD simulation indicated (-)-kusunokinin and pexidartinib (P31, a specific CSF1R binding compound) shared some extents of functional similarity in which (-)-kusunokinin bound CSF1R at the juxtamembrane (JM) region with aromatic amino acids similar to pexidartinib using π-π interaction, as well as hydrogen bond. Both P31 and (-)-kusunokinin moved into the same CSF1R region and W7 was a mutual key residue. However, the P31 binding site differed from the (-)-kusunokinin binding site. For in vitro study, the synthetic (±)-kusunokinin exhibited stronger cytotoxicity than picropodophyllotoxin, silibinin and etoposide on MCF-7 cells and represented less toxicity than picropodophyllotoxin and doxorubicin on L-929 and MCF-12A cells. Knocking down CSF1R using a specific siRNA combination with (±)-kusunokinin demonstrated levels of cell proliferation proteins slightly higher than siRNA-CSF1R treatment. However, siRNA-CSF1R combination with P31 represented the number of cell viability and cell proliferation proteins, like in the control groups (Lipofectamine and siRNA-Luciferase). Moreover, (±)-kusunokinin suppressed CSF1R and its downstream proteins, including AKT, CyclinD1 and CDK1. Meanwhile, both P31 and siRNA-CSF1R dramatically suppressed CSF1R, MEK1, AKT, ERK, CyclinB1, CyclinD1 and CDK1. Our overall results indicate that the mechanism of (±)-kusunokinin differed fairly from P31. We have concluded that (±)-kusunokinin inhibited breast cancer cell proliferation partially through the binding and suppression of CSF1R, which consequently affected AKT and its downstream molecules.

2016-08-25·Genome Announcements

Draft Genome Sequence of Phosphate-Solubilizing Bacterium Paraburkholderia tropica Strain P-31 Isolated from Pomegranate ( Punica granatum ) Rhizosphere

Article

作者: Selvakumar, Govindan ; Kaur, Chandandeep ; Ganeshamurthy, Arakalgud Nanjundiah

ABSTRACT We report the 8.9 Mb draft genome sequence of phosphate-solubilizing bacterium Paraburkholderia tropica strain P-31, isolated from pomegranate ( Punica granatum ) rhizosphere. The draft genome sequence of Paraburkholderia tropica strain P-31 consists of 8,881,246 bp with a G+C content of 64.7%, 8,039 protein-coding genes, and 49 RNAs.

2008-04-01·Microbiology and Immunology4区 · 医学

In silico prediction and immunological validation of common HLA‐DRB1‐restricted T cell epitopes of Candida albicans secretory aspartyl proteinase 2

4区 · 医学

Article

作者: Vladimir Brusic ; Chanvit Leelayuwat ; Sansanee C. Chaiyaroj ; Songsak Tongchusak

ABSTRACTSap2 is the most abundant virulence factor expressed during Candida infection, and the principal protein known to induce antibody response during Candida infection in humans. Its role in T‐cell activation however, has not yet been determined. Sequence analysis revealed that Sap2 contains two variable regions: Var1 and Var2. Computational predictions by the Hotspot Hunter program identified that Var1 contains three candidate T‐cell epitopes, whereas Var2 contains four. Thirty‐nine overlapping peptides of Sap2 were then synthesized, and tested for their ability to induce proliferation of PBMC from 12 donors. Peptides P11, P17 and P31 exhibited significantly higher proliferative indices when compared with those of other peptides or controls. P17 and P31 are located in the areas of prediction, while P11 is not. There were other peptides outside the prediction areas that could stimulate PBMC proliferation at low levels. Nevertheless, the proliferative noise caused by such peptides was ruled out by IL‐2 ELISpot analysis. Only P17 and P31 were shown to induce clonal proliferation of IFN‐γ producing lymphocytes, suggesting that these two peptides contain T cell epitopes. P11, which stimulated IL‐2 producing clones, contains a known B‐cell epitope. Interestingly, P17 and P31 elicited both Th1 and Th2 cell responses with significant numbers of IL‐13 secreting clones in response to stimulation. Taken together, the computer‐based T cell epitope prediction method could identify the immunogenic T cell epitopes of C. albicans Sap2 that promiscuously bind to the HLA‐DRB1 supertype.

100 项与 P-31 相关的药物交易

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