Xanthine Oxidase Inhibitory Triterpenoid and Phloroglucinol from Guttiferaceous Plants Inhibit Growth and Induced Apoptosis in Human NTUB1 Cells through a ROS-Dependent Mechanism

2011 ◽  
Vol 59 (1) ◽  
pp. 407-414 ◽  
Author(s):  
Kai-Wei Lin ◽  
A-Mei Huang ◽  
Huang-Yao Tu ◽  
Ling-Yi Lee ◽  
Chien-Chang Wu ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Induced Apoptosis ◽  
Dependent Mechanism

scholarly journals A p53-Phosphoinositide Signalosome Regulates Nuclear Akt Activation

2021 ◽  
Author(s):  
Mo Chen ◽  
Suyong Choi ◽  
Tianmu Wen ◽  
Changliang Chen ◽  
Narendra Thapa ◽  
...  
Keyword(s):  
Genotoxic Stress ◽  
Akt Pathway ◽  
Mutant P53 ◽  
Tumor Suppressor P53 ◽  
Wild Type ◽  
Akt Activation ◽  
Pi3k Inhibitors ◽  
Phosphoinositide 3 Kinase ◽  
Induced Apoptosis ◽  
Dependent Mechanism

The tumor suppressor p53 and the phosphoinositide 3-kinase (PI3K)-Akt pathway have fundamental roles in regulating cell growth, apoptosis and are frequently mutated in cancer. Here, we show that genotoxic stress induces nuclear Akt activation by a p53-dependent mechanism that is independent from the canonical membrane-localized PI3K-Akt pathway. Upon genotoxic stress a nuclear p53-PI3,4,5P3 complex is generated in regions devoid of membranes by a nuclear PI3K, and this complex recruits all the kinases required to activate Akt and phosphorylate FOXOs, inhibiting DNA damage-induced apoptosis. Wild-type p53 activates nuclear Akt in an on/off fashion upon stress, whereas mutant p53 stimulates high basal Akt activity, indicating a fundamental difference. The nuclear p53-phosphoinositide signalosome is distinct from the canonical membrane-localized pathway and insensitive to PI3K inhibitors currently in the clinic, underscoring its therapeutic relevance.

scholarly journals The Human Immunodeficiency Virus Type 1 Tat Protein Enhances Cryptosporidium parvum-Induced Apoptosis in Cholangiocytes via a Fas Ligand-Dependent Mechanism

2006 ◽  
Vol 75 (2) ◽  
pp. 684-696 ◽  
Author(s):  
Steven P. O'Hara ◽  
Aaron J. Small ◽  
Jeremy B. Nelson ◽  
Andrew D. Badley ◽  
Xian-Ming Chen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Cryptosporidium Parvum ◽  
Fas Ligand ◽  
Tat Protein ◽  
Immunodeficiency Virus ◽  
Induced Apoptosis ◽  
Hiv 1 ◽  
Dependent Mechanism

ABSTRACT While Cryptosporidium parvum infection of the intestine has been reported in both immunocompetent and immunocompromised individuals, biliary infection is seen primarily in adult AIDS patients and is associated with development of AIDS cholangiopathy. However, the mechanisms of pathogen-induced AIDS cholangiopathy remain unclear. Since we previously demonstrated that the Fas/Fas ligand (FasL) system is involved in paracrine-mediated C. parvum cytopathicity in cholangiocytes, we also tested the potential synergistic effects of human immunodeficiency virus type 1 (HIV-1) transactivator of transcription (Tat)-mediated FasL regulation on C. parvum-induced apoptosis in cholangiocytes by semiquantitative reverse transcription-PCR, immunoblotting, immunofluorescence analysis, and immunogold electron microscopy. H69 cells do not express CXCR4 and CCR5, which are receptors required for direct HIV-1 viral infection. However, recombinant biologically active HIV-1-associated Tat protein increased FasL expression in the cytoplasm of cholangiocytes without a significant increase in apoptosis. We found that C. parvum-induced apoptosis was associated with translocation of intracellular FasL to the cell membrane surface and release of full-length FasL from infected H69 cells. Tat significantly (P < 0.05) increased C. parvum-induced apoptosis in bystander cells in a dose-dependent manner. Moreover, Tat enhanced both C. parvum-induced FasL membrane translocation and release of full-length FasL. In addition, the FasL neutralizing antibody NOK-1 and the caspase-8 inhibitor Z-IETD-fmk both blocked C. parvum-induced apoptosis in cholangiocytes. The data demonstrated that HIV-1 Tat enhances C. parvum-induced cholangiocyte apoptosis via a paracrine-mediated, FasL-dependent mechanism. Our results suggest that concurrent active HIV replication, with associated production of Tat protein, and C. parvum infection synergistically increase cholangiocyte apoptosis and thus jointly contribute to AIDS-related cholangiopathies.

scholarly journals Alcohol Enhances Oxysterol-Induced Apoptosis in Human Endothelial Cells by a Calcium-Dependent Mechanism

2001 ◽  
Vol 21 (3) ◽  
pp. 439-444 ◽  
Author(s):  
Ioakim Spyridopoulos ◽  
Jörg Wischhusen ◽  
Björn Rabenstein ◽  
Petra Mayer ◽  
Dorothea I. Axel ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Human Endothelial Cells ◽  
Calcium Dependent ◽  
Induced Apoptosis ◽  
Dependent Mechanism

M1610 Aurora Kinase a Abrogates Drug-Induced Apoptosis Through Regulating p53 in AKT-Dependent Mechanism

2008 ◽  
Vol 134 (4) ◽  
pp. A-381-A-382
Author(s):  
Altaf Dar ◽  
Abbes Belkhiri ◽  
M. Blanca Piazuelo ◽  
Pelayo Correa ◽  
Alexander I. Zaika ◽  
...  
Keyword(s):  
Aurora Kinase ◽  
Drug Induced ◽  
Aurora Kinase A ◽  
Induced Apoptosis ◽  
Kinase A ◽  
Dependent Mechanism

scholarly journals P73 regulates cisplatin-induced apoptosis in ovarian cancer cells via a calcium/calpain-dependent mechanism

Oncogene ◽  
2011 ◽  
Vol 30 (41) ◽  
pp. 4219-4230 ◽  
Author(s):  
S Al-Bahlani ◽  
M Fraser ◽  
A Y C Wong ◽  
B S Sayan ◽  
R Bergeron ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Induced Apoptosis ◽  
Dependent Mechanism

Taurocholate feeding prevents CCl4-induced damage of large cholangiocytes through PI3-kinase-dependent mechanism

2003 ◽  
Vol 284 (2) ◽  
pp. G290-G301 ◽  
Author(s):  
Luca Marucci ◽  
Gianfranco Alpini ◽  
Shannon S. Glaser ◽  
Domenico Alvaro ◽  
Antonio Benedetti ◽  
...  
Keyword(s):  
Bile Acids ◽  
Bile Duct Ligation ◽  
Phosphatidylinositol 3 Kinase ◽  
Cytoprotective Effect ◽  
Drug Induced ◽  
Duct Ligation ◽  
Phosphorylated Akt ◽  
Induced Apoptosis ◽  
Dependent Mechanism

Bile acids are cytoprotective in hepatocytes by activating phosphatidylinositol-3-kinase (PI3-K) and its downstream signal AKT. Our aim was to determine whether feeding taurocholate to CCl4-treated rats reduces cholangiocyte apoptosis and whether this cytoprotective effect is dependent on PI3-K. Cholangiocyte proliferation, secretion, and apoptosis were determined in cholangiocytes from bile duct ligation (BDL), CCl4-treated BDL rats, and CCl4-treated taurocholate-fed rats. In vitro, we tested whether CCl4induces apoptosis and whether loss of cholangiocyte proliferation and secretion is dependent on PI3-K. The CCl4-induced cholangiocyte apoptosis and loss of cholangiocyte proliferation and secretion were reduced in CCl4-treated rats fed taurocholate. CCl4-induced cholangiocyte apoptosis, loss of cholangiocytes secretion, and proliferation were prevented by preincubation with taurocholate. Taurocholate cytoprotective effects were ablated by wortmannin. Taurocholate prevented, in vitro, CCl4-induced decrease of phosphorylated AKT protein expression in cholangiocytes. The cytoprotective effects of taurocholate on CCl4 effects on cholangiocyte proliferation and secretion were abolished by wortmannin. Taurocholate protects cholangiocytes from CCl4-induced apoptosis by a PI3-K-dependent mechanism. Bile acids are important in the prevention of drug-induced ductopenia in cholangiopathies.

PPARgamma ligand-induced apoptosis through a p53-dependent mechanism in human gastric cancer cells

2003 ◽  
Vol 94 (4) ◽  
pp. 338-343 ◽  
Author(s):  
Miho Nagamine ◽  
Toshikatsu Okumura ◽  
Satoshi Tanno ◽  
Mitsuko Sawamukai ◽  
Wataru Motomura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Induced Apoptosis ◽  
Dependent Mechanism

Involvement of the Mitochondria-Caspase Pathway in HeLa Cell Death Induced by 2-Ethanolamino-2-Demethoxy-17-Ethanolimino-Hypocrellin B (EAHB)-Mediated Photodynamic Therapy

2012 ◽  
Vol 31 (5) ◽  
pp. 483-492 ◽  
Author(s):  
Zhixiang Zhou ◽  
Chen Zhao ◽  
Wei Liu ◽  
Qianqian Li ◽  
Lina Zhang ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Hela Cells ◽  
Caspase 3 ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Hypocrellin B ◽  
Confocal Fluorescence ◽  
Cellular Apoptosis ◽  
Induced Apoptosis ◽  
Dependent Mechanism

In order to elucidate the mechanism of cytotoxicity photoinduced by 2-ethanolamino-2-demethoxy-17-ethanolimino-hypocrellin B (EAHB), a derivative of hypocrellin B (HB), cellular uptake, subcellular localization as well as photodynamic therapy (PDT) efficiency of EAHB, and cell apoptosis photoinduced by EAHB were investigated in HeLa cells by laser confocal fluorescence microscopy, 3-(4,5-Dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, flow cytometry, DNA fragmentation on agarose gel, and Western blot. The results showed EAHB was distributed throughout the cytoplasm of the cell, with no detectable penetration into the nucleus. The proportion of dead cells increased with increases in both the dosage of light and the concentration of EAHB. Its phototoxicity to HeLa cells proceeded via apoptosis. The EAHB-PDT treatment induced a cytochrome c release from the mitochondria into the cytosol followed by the activation of both caspase 3 and caspase 9 in HeLa cells. The results suggested that EAHB-PDT treatment induced apoptosis in HeLa cells, and the cellular apoptosis involved a mitochondria-/caspase-dependent mechanism.

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