Reactive Oxygen Species (ROS) can induce small molecules that use the altered redox state in cancer cells that will be more vulnerable than normal cells to agents with high levels of ROS as well as antioxidant enzymes. Piperlongumine(PL), a natural alkaloid from Piper longum L, can increase the level of ROS and selectively kills cancer cells, which is also a TrxR1 inhibitor with suppressive activity against gastric cancer and a novel inhibitor of CRM1 as well as an inhibitor of PI3K/Akt/mTOR in human breast cancer cells. The average IC50 value of piperlongumine in different cell types is about 5μM. Piperlongumine with concentration range of 0.1–20 μM induced a concentration and time-dependent decrease in the viability of PANC-1, MIA PaCa-2, and BxPC-3, with IC50 values of 4.2, 4.6, and 4.2 μM, respectively at 72 h. MIA PaCa-2 and BxPC-3 cells were particularly sensitive to piperlongumine, and no cells survived for the 5 and 10 μM treatments. PANC-1, MIA PaCa-2, and BxPC-3 cells treated with 10 μM PPLGM for 6 h followed by staining for 30 min, the production
of ROS in all three cell lines increased. Three ovarian cancer cell lines A2780, OVCAR3, and SKOV3 and human embryonic kidney cell line HEK293T were treated with either DMSO or PL range from 1 to 100 μM for 72 hr, the IC50 values of PL afer 72 hr exposure were 6.18 μM, 6.20 μM, and 8.20 μM in A2780, OVCAR3, and SKOV3, respectively while it is 60.23 μM to HEK293T. In addition, PL treatment mostly induced apoptosis in OVCAR3 cells. OVCAR3 cells treated with PL (3 μM and 10 μM for 24 hr and 48 hr) showed that the subG1 and G2/M groups were dose- and time dependently increased. Furthermore, HepG2 cells were treated with 2 mM of PL to determine its ability to activate AMPK. PL increased Thr172 phosphorylation and led to a dose-dependent increase in phosphorylation of AMPK and acetyl-CoA carboxylase.
作用机制
Piperlongumine can induce cell autophagy and cell death, inhibit cell proliferation and survival.
Piperlongumine/荜茇酰胺 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Primary neurons
0.1 µM
24 hours
PLG reduced cell injury and cell death induced by rotenone
Autophagy. 2018;14(5):845-861.
293T cells
0.1 µM
8 hours
Induced CDK9 degradation
Cell Chem Biol. 2023 Feb 16;30(2):203-213.e17.
K562 cells
0.1 µM
8 hours
Induced CDK9 degradation
Cell Chem Biol. 2023 Feb 16;30(2):203-213.e17.
MOLT4 cells
0.1 µM
16 hours
Induced CDK9 degradation
Cell Chem Biol. 2023 Feb 16;30(2):203-213.e17.
High-grade glioma sphere cultures
0-10 mM
1-3 days
Piperlongumine treatment increased ROS levels and preferentially killed HGG cells with little effect in normal brain cells.
Neuro Oncol. 2014 Oct;16(10):1354-64.
Neural stem cell (NSC) sphere cultures
0-10 mM
1-3 days
Piperlongumine treatment had little effect on the growth of neural stem cells.
Neuro Oncol. 2014 Oct;16(10):1354-64.
Astrocytes
0-10 mM
1-3 days
Piperlongumine treatment at the highest dose of 10 mM suppressed the growth of astrocyte cultures.
Neuro Oncol. 2014 Oct;16(10):1354-64.
SK-N-SH cells
0.1 - 2.5 µM
24 hours
PLG partially reversed the decrease in cell viability and increase in cytotoxicity induced by rotenone
Autophagy. 2018;14(5):845-861.
Primary neurons
0.1 µM
24 hours
PLG reduced cell injury and cell death rate induced by rotenone
Autophagy. 2018;14(5):845-861.
SK-N-SH cells
0.1 - 2.5 µM
24 hours
PLG partly abrogated the reduction in cell viability and enhancement in cytotoxicity induced by rotenone
Autophagy. 2018;14(5):845-861.
A549 cells
0 to 50 µM
24 hours
To evaluate the cytotoxicity of Piperlongumine on A549 cells, the results showed that Piperlongumine has cytotoxicity on A549 cells in the range of 0 to 50 µM.
Antioxidants (Basel). 2022 Apr 4;11(4):710.
HCT116 cells
0 to 50 µM
24 hours
To evaluate the cytotoxicity of Piperlongumine on HCT116 cells, the results showed that Piperlongumine has cytotoxicity on HCT116 cells in the range of 0 to 50 µM.
Antioxidants (Basel). 2022 Apr 4;11(4):710.
HepG2 cells
0 to 50 µM
24 hours
To evaluate the cytotoxicity of Piperlongumine on HepG2 cells, the results showed that Piperlongumine has cytotoxicity on HepG2 cells in the range of 0 to 50 µM.
Antioxidants (Basel). 2022 Apr 4;11(4):710.
MCF-7 cells
0 to 50 µM
24 hours
To evaluate the cytotoxicity of Piperlongumine on MCF-7 cells, the results showed that Piperlongumine has cytotoxicity on MCF-7 cells in the range of 0 to 50 µM.
Antioxidants (Basel). 2022 Apr 4;11(4):710.
Piperlongumine/荜茇酰胺 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL mice
Rotenone-induced Parkinson's disease model
Oral
2 and 4 mg/kg
Once daily for 4 weeks
PLG attenuated motor deficits in mice and prevented the loss of dopaminergic neurons induced by rotenone
Autophagy. 2018;14(5):845-861.
C57BL/6J mice
Chemotherapy-induced cognitive impairment model
Intraperitoneal injection
2 mg/kg
Weekly for 12 weeks
To investigate the neuroprotective role of Piperlongumine in chemotherapy-induced cognitive impairment. Results showed that TAC/PL co-treated mice did not exhibit measurable social memory deficits during social memory testing, indicating that Piperlongumine protects against TAC-induced social memory impairment.
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