Chelerythrine chloride from Macleaya cordata induces growth inhibition and apoptosis in human gastric cancer BGC-823 cells

This study aimed to investigate the ability of chelerythrine chloride(CHE),the main active ingredient of Macleaya cordata,to induce apoptosis in human gastric cancer BGC-823 cells.The results demonstrate that CHE inhibits cell proliferation in a time-and dose-dependent manner with accompanying S phase arrest.It also induces apoptosis by a mechanism involving a reduction in the mitochondrial mem brane potential,the release of cytochrome c,activation of caspase 3 and cleavage of poly-ADP-ribose polymerase.In addition,CHE-induced apoptosis is accompanied by down-regulation of Bcl-x1 and Bcl-2 proteins with no change in the levels of Bax proteins.Taken together,the results support the development of CHE as a potentially useful anticancer drug for the treatment of gastric cancer.

Erianin suppresses constitutive activation of MAPK signaling pathway by inhibition of CRAF and MEK1/2

Constitutive activation of RAS-RAF-MEK-ERK signaling pathway(MAPK pathway)frequently occurs in many cancers harboring RAS or RAF oncogenic mutations.Because of the paradoxical activation induced by a single use of BRAF or MEK inhibitors,dual-target RAF and MEK treatment is thought to be a promising strategy.In this work,we evaluated erianin is a novel inhibitor of CRAF and MEK1/2 kinases,thus suppressing constitutive activation of the MAPK signaling pathway induced by BRAF V600E or RAS mutations.KinaseProfiler enzyme profiling,surface plasmon resonance(SPR),isothermal titration calorimetry(ITC),cellular thermal shift assay,computational docking,and molecular dynamics simulations were utilized to screen and identify erianin binding to CRAF and MEK1/2.Kinase assay,luminescent ADP detection assay,and enzyme kinetics assay were investigated to identify the efficiency of erianin in CRAF and MEK1/2 kinase activity.Notably,erianin suppressed BRAF V600E or RAS mutant melanoma and colorectal cancer cell by inhibiting MEK1/2 and CRAF but not BRAF kinase activity.Moreover,erianin attenuated melanoma and colorectal cancer in vivo.Overall,we provide a promising leading compound for BRAF V600E or RAS mutant melanoma and colorectal cancer through dual targeting of CRAF and MEK1/2.

Regulation of noncoding RNAs in innate lymphoid cells

Innate lymphoid cells(ILCs)have been defined in recent years and are important effector cells against pathogens and critical regulators in maintaining tissue homeostasis[1].Noncoding RNAs(ncRNAs),such as circular RNAs(circRNAs),long noncoding RNAs(lncRNAs),and microRNAs(miRNAs),in ILCs are emerging and have been described to function in ILC biology.These ncRNAs are distributed with unique patterns in ILCs and function in different molecular mechanisms.Accumulating research evidence demonstrates that ncRNA dysregulation links ILC-mediated immune responses and diseases.