Nuclear factor-kappaB sensitizes to benzyl isothiocyanate-induced antiproliferation in p53-deficient colorectal cancer cells.

Benzyl isothiocyanate (BITC), a dietary isothiocyanate derived from cruciferous vegetables, inhibits the proliferation of colorectal cancer cells, most of which overexpress ß-catenin as a result of mutations in the genes for adenomatous polyposis coli or mutations in ß-catenin itself. Because nuclear factor-κB (NF-κB) is a plausible target of BITC signaling in inflammatory cell models, we hypothesized that it is also involved in BITC-inhibited proliferation of colorectal cancer cells. siRNA-mediated knockdown of the NF-κB p65 subunit significantly decreased the BITC sensitivity of human colorectal cancer HT-29 cells with mutated p53 tumor suppressor protein. Treating HT-29 cells with BITC induced the phosphorylation of IκB kinase, IκB-α and p65, the degradation of IκB-α, the translocation of p65 to the nucleus and the upregulation of NF-κB transcriptional activity. BITC also decreased ß-catenin binding to a positive cis element of the cyclin D1 promoter and thus inhibited ß-catenin-dependent cyclin D1 transcription, possibly through a direct interaction between p65 and ß-catenin. siRNA-mediated knockdown of p65 confirmed that p65 negatively affects cyclin D1 expression. On the other hand, when human colorectal cancer HCT-116 cells with wild-type p53 were treated with BITC, translocation of p65 to the nucleus was inhibited rather than enhanced. p53 knockout increased the BITC sensitivity of HCT-116 cells in a p65-dependent manner, suggesting that p53 negatively regulates p65-dependent effects. Together, these results identify BITC as a novel type of antiproliferative agent that regulates the NF-κB pathway in p53-deficient colorectal cancer cells.

Cyclic adenosine 5'-diphosphoribose (cADPR) cyclic guanosine 3',5'-monophosphate positively function in Ca(2+) elevation in methyl jasmonate-induced stomatal closure, cADPR is required for methyl jasmonate-induced ROS accumulation NO production in guard cells.

Methyl jasmonate (MeJA) signalling shares several signal components with abscisic acid (ABA) signalling in guard cells. Cyclic adenosine 5'-diphosphoribose (cADPR) and cyclic guanosine 3',5'-monophosphate (cGMP) are second messengers in ABA-induced stomatal closure. In order to clarify involvement of cADPR and cGMP in MeJA-induced stomatal closure in Arabidopsis thaliana (Col-0), we investigated effects of an inhibitor of cADPR synthesis, nicotinamide (NA), and an inhibitor of cGMP synthesis, LY83583 (LY, 6-anilino-5,8-quinolinedione), on MeJA-induced stomatal closure. Treatment with NA and LY inhibited MeJA-induced stomatal closure. NA inhibited MeJA-induced reactive oxygen species (ROS) accumulation and nitric oxide (NO) production in guard cells. NA and LY suppressed transient elevations elicited by MeJA in cytosolic free Ca(2+) concentration ([Ca(2+)]cyt) in guard cells. These results suggest that cADPR and cGMP positively function in [Ca(2+)]cyt elevation in MeJA-induced stomatal closure, are signalling components shared with ABA-induced stomatal closure in Arabidopsis, and that cADPR is required for MeJA-induced ROS accumulation and NO production in Arabidopsis guard cells.

Adult onset Still's disease associated hemophagocytosis.

Reactive hemophagocytosis is characterized by the activation of histiocytes with prominent hemophagocytosis in the reticuloendothelial system, and usually occurs in association with underlying disorders such as viral or bacterial infection and malignancy. We describe 3 cases of adult onset Still's disease (AOSD) who developed hemophagocytosis in bone marrow. Extensive studies could not identify any viral infection or other known underlying disorders for reactive hemophagocytosis except for active AOSD. Although the causative mechanisms of reactive hemophagocytosis in AOSD are not clear, our cases suggest the possibility of AOSD associated hemophagocytosis.