Aconitine induces cell apoptosis via mitochondria and death receptor signaling pathways in hippocampus cell line

Polyphyllin has been reported to exhibit anticancer effects against various types of cancer via the proapoptotic signaling pathway. The aim of the present study was to investigate the role of the endoplasmic reticulum stress and death receptor signaling pathways in PPI-induced apoptosis of human hepatocellular carcinoma HepG2 cells. Analysis demonstrated that PPI could significantly inhibit the proliferation and induce apoptosis of HepG2 cells in a dose- and time-dependent manner. Investigation into the molecular mechanism of PPI indicated that PPI notably mediated ER stress activation via IRE-1 overexpression and activation of the caspase-12 to protect HepG2 cells against apoptosis. In addition, PPI markedly induced the expression of death receptors signaling pathways-associated factors, including tumor necrosis factor (TNF) receptor 1/TNF-αand FAS/FASL. Additionally, suppression of the death receptor signaling pathways with a caspase-8 inhibitor, Z-IETD-FMK, revealed an increase in the death rate and apoptotic rate of HepG2 cells. Collectively, the findings of the present study suggested that the ER stress and death receptor signaling pathways were associated with PPI-induced HepG2 cell apoptosis; however, endoplasmic reticulum stress may serve a protective role in this process. The combination of PPI and Z-IETD-FMK may activate necroptosis, which enhances apoptosis. Therefore, the results of the present study may improve understanding regarding the roles of signaling pathways in PPI regulated apoptosis and contribute to the development of novel therapies for the treatment of HCC.

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Sub-Lethal Irradiation of Human Colorectal Tumor Cells Imparts Enhanced and Sustained Susceptibility to Multiple Death Receptor Signaling Pathways

PLoS ONE ◽

10.1371/journal.pone.0031762 ◽

2012 ◽

Vol 7 (2) ◽

pp. e31762 ◽

Cited By ~ 21

Author(s):

Victoria Ifeadi ◽

Charlie Garnett-Benson

Keyword(s):

Signaling Pathways ◽

Tumor Cells ◽

Death Receptor ◽

Colorectal Tumor ◽

Receptor Signaling ◽

Death Receptor Signaling ◽

Lethal Irradiation

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Cross-Talk Between Autophagy and Death Receptor Signaling Pathways

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging ◽

10.1016/b978-0-12-805421-5.00004-5 ◽

2016 ◽

pp. 119-133

Author(s):

Kelly Airiau ◽

Mojgan Djavaheri-Mergny

Keyword(s):

Signaling Pathways ◽

Cross Talk ◽

Death Receptor ◽

Receptor Signaling ◽

Death Receptor Signaling

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Beyond apoptosis: nonapoptotic cell death in physiology and disease

Biochemistry and Cell Biology ◽

10.1139/o05-065 ◽

2005 ◽

Vol 83 (5) ◽

pp. 579-588 ◽

Cited By ~ 45

Author(s):

Claudio A Hetz ◽

Vicente Torres ◽

Andrew F.G Quest

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Death Receptor ◽

Receptor Signaling ◽

Family Analysis ◽

Caspase Family ◽

Death Receptor Signaling ◽

Apoptotic Pathways ◽

Nonapoptotic Cell Death ◽

High Degree

Apoptosis is a morphologically defined form of programmed cell death (PCD) that is mediated by the activation of members of the caspase family. Analysis of death-receptor signaling in lymphocytes has revealed that caspase-dependent signaling pathways are also linked to cell death by nonapoptotic mechanisms, indicating that apoptosis is not the only form of PCD. Under physiological and pathological conditions, cells demonstrate a high degree of flexibility in cell-death responses, as is reflected in the existence of a variety of mechanisms, including necrosis-like PCD, autophagy (or type II PCD), and accidental necrosis. In this review, we discuss recent data suggesting that canonical apoptotic pathways, including death-receptor signaling, control caspase-dependent and -independent cell-death pathways.Key words: apoptosis, necrosis, nonapoptotic programmed cell death, death receptors, ceramides.

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