Inhibition of the PI3 kinase/Akt pathway enhances doxorubicin-induced apoptotic cell death in tumor cells in a p53-dependent manner

2006 ◽  
Vol 340 (2) ◽  
pp. 560-566 ◽  
Author(s):  
Yusuke Fujiwara ◽  
Kei Kawada ◽  
Daiki Takano ◽  
Susumu Tanimura ◽  
Kei-ichi Ozaki ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Apoptotic Cell ◽  
Pi3 Kinase ◽  
Apoptotic Cell Death ◽  
Akt Pathway ◽  
Dependent Manner

scholarly journals Curcumin Induces Apoptotic Cell Death via Inhibition of PI3-Kinase/AKT Pathway in B-Precursor Acute Lymphoblastic Leukemia

2019 ◽  
Vol 9 ◽  
Author(s):  
Shilpa Kuttikrishnan ◽  
Kodappully S. Siveen ◽  
Kirti S. Prabhu ◽  
Abdul Quaiyoom Khan ◽  
Eiman I. Ahmed ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lymphoblastic Leukemia ◽  
Apoptotic Cell ◽  
Lymphoblastic Leukemia ◽  
Pi3 Kinase ◽  
Apoptotic Cell Death ◽  
Akt Pathway

scholarly journals Nucleotide Biosynthesis Links Glutathione Metabolism to Ferroptosis Sensitivity

2021 ◽  
Author(s):  
Amy Tarangelo ◽  
Joon Tae Kim ◽  
Jonathan Z Long ◽  
Scott J Dixon
Keyword(s):  
Cell Death ◽  
De Novo ◽  
Apoptotic Cell ◽  
Lipid Peroxides ◽  
Nucleotide Metabolism ◽  
Apoptotic Cell Death ◽  
Death Process ◽  
Glutathione Metabolism ◽  
Dependent Manner ◽  
Nucleotide Synthesis

Nucleotide synthesis is a metabolically demanding process essential for cell division. Several anti-cancer drugs that inhibit nucleotide metabolism induce apoptosis. How inhibition of nucleotide metabolism impacts non-apoptotic cell death is less clear. Here, we report that inhibition of nucleotide metabolism by the p53 pathway is sufficient to suppress the non-apoptotic cell death process of ferroptosis. Mechanistically, stabilization of wild-type p53 and induction of the p53 target gene CDKN1A (p21) leads to decreased expression of the ribonucleotide reductase (RNR) subunits RRM1 and RRM2. RNR is the rate-limiting enzyme of de novo nucleotide synthesis that reduces ribonucleotides to deoxyribonucleotides in a glutathione-dependent manner. Direct inhibition of RNR conserves glutathione which can then be used to limit the accumulation of toxic lipid peroxides, preventing the onset of ferroptosis. These results support a mechanism linking p53-dependent regulation of nucleotide metabolism to non-apoptotic cell death.

Non-apoptotic cell death in malignant tumor cells and natural compounds

2018 ◽  
Vol 420 ◽  
pp. 210-227 ◽  
Author(s):  
Jing Ye ◽  
Ruonan Zhang ◽  
Fan Wu ◽  
Lijuan Zhai ◽  
Kaifeng Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Malignant Tumor ◽  
Apoptotic Cell ◽  
Natural Compounds ◽  
Apoptotic Cell Death

scholarly journals Shiga Toxins Activate the NLRP3 Inflammasome Pathway To Promote Both Production of the Proinflammatory Cytokine Interleukin-1β and Apoptotic Cell Death

2015 ◽  
Vol 84 (1) ◽  
pp. 172-186 ◽  
Author(s):  
Moo-Seung Lee ◽  
Haenaem Kwon ◽  
Eun-Young Lee ◽  
Dong-Jae Kim ◽  
Jong-Hwan Park ◽  
...  
Keyword(s):  
Cell Death ◽  
Nlrp3 Inflammasome ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Interleukin 1Β ◽  
Dependent Manner ◽  
Shiga Toxins ◽  
Caspase 1 ◽  
Immune Signaling Pathway ◽  
Tnf Α

Shiga toxin (Stx)-mediated immune responses, including the production of the proinflammatory cytokines tumor necrosis-α (TNF-α) and interleukin-1β (IL-1β), may exacerbate vascular damage and accelerate lethality. However, the immune signaling pathway activated in response to Stx is not well understood. Here, we demonstrate that enzymatically active Stx, which leads to ribotoxic stress, triggers NLRP3 inflammasome-dependent caspase-1 activation and IL-1β secretion in differentiated macrophage-like THP-1 (D-THP-1) cells. The treatment of cells with a chemical inhibitor of glycosphingolipid biosynthesis, which suppresses the expression of the Stx receptor globotriaosylceramide and subsequent endocytosis of the toxin, substantially blocked activation of the NLRP3 inflammasome and processing of caspase-1 and IL-1β. Processing and release of both caspase-1 and IL-1β were significantly reduced or abolished in Stx-intoxicated D-THP-1 cells in which the expression of NLRP3 or ASC was stably knocked down. Furthermore, Stx mediated the activation of caspases involved in apoptosis in an NLRP3- or ASC-dependent manner. In Stx-intoxicated cells, the NLRP3 inflammasome triggered the activation of caspase-8/3, leading to the initiation of apoptosis, in addition to caspase-1-dependent pyroptotic cell death. Taken together, these results suggest that Stxs trigger the NLRP3 inflammasome pathway to release proinflammatory IL-1β as well as to promote apoptotic cell death.

scholarly journals Chemoproteomic Discovery of a Ritanserin-Targeted Kinase Network Mediating Apoptotic Cell Death of Lung Tumor Cells

2018 ◽  
Vol 94 (5) ◽  
pp. 1246-1255 ◽  
Author(s):  
Sean T. Campbell ◽  
Caroline E. Franks ◽  
Adam L. Borne ◽  
Myungsun Shin ◽  
Liuzhi Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Lung Tumor ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death

Apoptosis And Resistance To Anti-Microtubule Agents

1998 ◽  
Vol 4 (S2) ◽  
pp. 1036-1037
Author(s):  
M. C. Willingham
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Mitotic Spindles ◽  
Trade Name ◽  
Anti Cancer ◽  
M Phase ◽  
Target Treatment ◽  
Microtubule Networks

Several clinically important anti-cancer agents exert their effects on tumor cells through interference with the function of microtubules. In addition to the Vinca alkaloids, such as vinblastine and vincristine, the taxanes, such as paclitaxel (Trade Name: Taxol), kill tumor cells through a microtubular target. Treatment with taxol leads to the inability of microtubules to depolymerize, leading to the formation of large intracellular microtubular bundles. In tumor cells that progress through the cell cycle, this leads to the inability of these cells to disassembly interphase microtubule networks and a failure to form functional mitotic spindles. These cells arrest in M phase, from which they eventually progress, either by the induction of apoptotic cell death, or by micronucleation and the formation of tetraploid cells. There is also the possibility that taxol has other effects on the regulation of genes or other systems to enhance cell killing, perhaps through lowering the threshold of cells to the induction of apoptotic cell death.

scholarly journals Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways

2005 ◽  
Vol 12 (10) ◽  
pp. 1329-1343 ◽  
Author(s):  
R D Almeida ◽  
B J Manadas ◽  
C V Melo ◽  
J R Gomes ◽  
C S Mendes ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Pi3 Kinase ◽  
Apoptotic Cell Death

scholarly journals Antiviral effect of dehydroepiandrosterone on Japanese encephalitis virus infection

2005 ◽  
Vol 86 (9) ◽  
pp. 2513-2523 ◽  
Author(s):  
Chia-Che Chang ◽  
Yen-Chuan Ou ◽  
Shue-Ling Raung ◽  
Chun-Jung Chen
Keyword(s):  
Cell Death ◽  
Japanese Encephalitis Virus ◽  
Japanese Encephalitis ◽  
Apoptotic Cell ◽  
Antiviral Effect ◽  
Encephalitis Virus ◽  
Apoptotic Cell Death ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Japanese Encephalitis Virus Infection

Japanese encephalitis virus (JEV), which causes neurological disorders, completes its life cycle and triggers apoptotic cell death in infected cells. Dehydroepiandrosterone (DHEA), an adrenal-derived steroid, has been implicated in protection against neurotoxicity and protection of animals from viral-induced encephalitis, resulting in an increased survival rate of the animals. Currently, the mechanisms underlying the beneficial effects of DHEA against the virus are largely unknown. In this study, DHEA suppression of JEV replication and virus-induced apoptosis in murine neuroblastoma (N18) cells was investigated. It was found that DHEA suppressed JEV-induced cytopathic effects, JEV-induced apoptotic cell death and JEV propagation in a concentration-dependent manner. Antiviral activity was more efficient in cultures treated with DHEA immediately after viral adsorption compared with that in cultures receiving delayed administration after adsorption or transient exposure before adsorption. JEV-induced cytotoxicity was accompanied by the inactivation of extracellular signal-regulated protein kinase (ERK). Inactivation of ERK by JEV infection was reversed by DHEA. When cells were treated with the ERK inhibitor U0126, DHEA lost its antiviral effect. Activation of ERK by anisomycin mimicked the action of DHEA in suppressing JEV-induced cytotoxicity. DHEA-related compounds, such as its sulfate ester (DHEAS) and pregnenolone, were unable to suppress JEV-induced cytotoxicity and ERK inactivation. The hormone-receptor antagonists ICI 182780 and flutamide failed to abrogate the antiviral effect of DHEA. These findings suggest that the antiviral effect of DHEA is not linked directly to the genomic steroid-receptor pathways and suggest that the signalling pathways of ERK play a role in the antiviral action of DHEA.

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