Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.4.2.30 (
PARP
)
13,611
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Deoxypodophyllotoxin
(
DPT
), a natural microtubule destabilizer, was isolated from Anthriscus sylvestris, and a few studies have reported its anti-cancer effect. However, the in vivo antitumor efficacy of
DPT
is currently indeterminate. In this study, we investigated the anti-gastric cancer effects of
DPT
both in vitro and in vivo. Our data showed that
DPT
inhibited cancer cell proliferation and induced G2/M cell cycle arrest accompanied by an increase in apoptotic cell death in SGC-7901 cancer cells. In addition,
DPT
caused cyclin B1, Cdc2 and Cdc25C to accumulate, decreased the expression of Bcl-2 and activated caspase-3 and
PARP
, suggesting that caspase-mediated pathways were involved in
DPT
-induced apoptosis. Animal studies revealed that
DPT
significantly inhibited tumor growth and decreased microvessel density (MVD) in a xenograft model of gastric cancer. Taken together, our findings provide a framework for further exploration of
DPT
as a novel chemotherapeutic for human gastric cancer.
...
PMID:Deoxypodophyllotoxin induces G2/M cell cycle arrest and apoptosis in SGC-7901 cells and inhibits tumor growth in vivo. 2560 54
Parthanatos is a new form of programmed cell death that is regulated by hyper-activated
PARP-1
, and is emerging as a new strategy to kill cancer cells.
Deoxypodophyllotoxin
(
DPT
) is a natural chemical that is found to induce cancer cell death, in which the role of parthanatos is unknown. Thus, we investigated this issue in this study by using glioma cell lines and mice model of xenograft glioma. We found that
DPT
induced glioma cell death in vitro and inhibited the growth of xenograft glioma in vivo, which was accompanied with parthanatos-related biochemical events including expressional upregulation of
PARP-1
, cytoplasmic accumulation of PAR polymer, and nuclear translocation of AIF. In vitro study revealed that genetic knockdown of
PARP-1
with small interfering RNA attenuated
DPT
-induced elevation in the cytoplasmic PAR-polymer and the nuclear AIF, as well as protected glioma cells against the toxicity of
DPT
. Further, antioxidant NAC, as well as
PARP-1
inhibitor 3AB, not only alleviated the overproduction of ROS caused by
DPT
, but also reversed the above-mentioned biochemical events, maintained mitochondrial membrane potential and rescued glioma cells death. Therefore, we demonstrated that deoxypodophyllotoxin triggered parthanatos in glioma cells via induction of excessive ROS.
...
PMID:Deoxypodophyllotoxin triggers parthanatos in glioma cells via induction of excessive ROS. 2668 70
