The biochemical phenomenon defined as poly adenosine diphosphate (ADP)-ribosylation (PARylation) is essential for the progression of pancreatic cancer. However, the excessive accumulation of poly ADP-ribose (PAR) induces apoptosis-inducing factor (AIF) release from mitochondria and energy deprivation resulting in the caspase-independent death of cancer cells.To investigate whether sustained calcium supply could induce an anticancer effect on pancreatic cancer by PAR accumulation.Two pancreatic cancer cell lines, AsPC-1 and CFPAC-1 were used for the study. Calcium influx and mitochondrial reactive oxygen species (ROS) were observed by fluorescence staining. Changes in enzyme levels, as well as PAR accumulation and energy metabolism, were measured using assay kits. AIF-dependent cell death was investigated followed by confirming in vivo anticancer effects by sustained calcium administration.Mitochondrial ROS levels were elevated with increasing calcium influx into pancreatic cancer cells. Then, excess PAR accumulation, decreased PAR glycohydrolase and ADP-ribosyl hydrolase 3 levels, and energy deprivation were observed. In vitro and in vivo antitumor effects were confirmed to accompany elevated AIF levels.This study visualized the potential anticancer effects of excessive PAR accumulation by sustained calcium supply on pancreatic cancer, however elucidating a clear mode of action remains a challenge, and it should be accompanied by further studies to assess its potential for clinical application.
The possible gene transfer from transgenic chili pepper to soil bacteria in rhizosphere was evaluated. DNA was extracted from rhizosphere soil collected from growing transgenic chili pepper (Capsicum annuum L.) resistant to cucumber mosaic virus (CMV) and control line, and PCR analysis was performed with specific primer for transgene in the transgenic chili pepper. The results of the PCR targeting NPTII gene indicated that the transgene was present in the rhizosphere soil samples in all collecting times. To investigate the cause of the transgene detection in the samples, we isolated microorganisms from the soil and cultured them on bacterial and fungal medium containing kanamycin. About 430 thousands of bacterial colonies and 160 thousands of fungal colonies were investigated, however, colonies resistant to kanamycin were not detected, indicating gene transfer from transgenic chili pepper to culturable rhizosphere soil microorganisms was not occurred in the present study.
p53 and Notch-1 play important roles in breast cancer biology. Notch-1 inhibits p53 activity in cervical and breast cancer cells. Conversely, p53 inhibits Notch activity in T-cells but stimulates it in human keratinocytes. Notch co-activator MAML1 binds p53 and functions as a p53 co-activator. We studied the regulation of Notch signaling by p53 in MCF-7 cells and normal human mammary epithelial cells (HMEC). Results show that overexpression of p53 or activation of endogenous p53 with Nutlin-3 inhibits Notch-dependent transcriptional activity and Notch target expression in a dose-dependent manner. This effect could be partially rescued by transfection of MAML1 but not p300. Standard and quantitative co-immunoprecipitation experiments readily detected a complex containing p53 and Notch-1 in MCF-7 cells. Formation of this complex was inhibited by dominant negative MAML1 (DN-MAML1) and stimulated by wild-type MAML1. Standard and quantitative far-Western experiments showed a complex including p53, Notch-1, and MAML1. Chromatin immunoprecipitation (ChIP) experiments showed that p53 can associate with Notch-dependent HEY1 promoter and this association is inhibited by DN-MAML1 and stimulated by wild-type MAML1. Our data support a model in which p53 associates with the Notch transcriptional complex (NTC) in a MAML1-dependent fashion, most likely through a p53-MAML1 interaction. In our cellular models, the effect of this association is to inhibit Notch-dependent transcription. Our data suggest that p53-null breast cancers may lack this Notch-modulatory mechanism, and that therapeutic strategies that activate wild-type p53 can indirectly cause inhibition of Notch transcriptional activity.
Effect of antioxidants on humoral immune responses, such as butylated hydroxytoluene (BHT), n-propyl gallate (PG) and dimethyl sulfoxide (DMSO) is suppression in in vitro antibody production. These antioxidants all inhibited T-dependent B cell response, not T-independent and polyclonal B cell response. These data suggest that antioxidants suppress humoral immunity by suppression of regulation of T cells or action of macrophages on B cells, not by direct suppression of B cells. The other possible explanation for antioxidant action is the lack of T-B cell contact required for the triggering of the B cell response with T-dependent antigens.
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