Piperlongumine, a natural alkaloid from Piper longum L., increases the level of reactive oxygen species (ROS) and selectively kills cancer cells. It is a direct TrxR1 inhibitor with suppressive activity against gastric cancer and an inhibitor ofCRM1 and is also an inhibitor of PI3K/Akt/mTOR in human breast cancer cells.
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 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
A375 cells
Proliferation assay
72 h
Antiproliferative activity against human A375 cells after 72 hrs by MTT assay, EC50=6.17 μM
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A549 cells
Proliferation assay
72 h
Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, EC50=12.2 μM
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HaCaT cells
Proliferation assay
72 h
Antiproliferative activity against human HaCaT cells after 72 hrs by MTT assay, EC50=4.46 μM
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HCT116 cells
Cytotoxicity assay
72 h
Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay, IC50=6.04 μM
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