Piperlongumine inhibits lung tumor growth via inhibition of nuclear factor kappa B signaling pathway

Abstract

Piperlongumine has anti-cancer activity in numerous cancer cell lines via various signaling pathways. But there has been no study regarding the mechanisms of PL on the lung cancer yet. Thus, we evaluated the anti-cancer effects and possible mechanisms of PL on non-small cell lung cancer (NSCLC) cells in vivo and in vitro. Our findings showed that PL induced apoptotic cell death and suppressed the DNA binding activity of NF-κB in a concentration dependent manner (0–15 μM) in NSCLC cells. Docking model and pull down assay showed that PL directly binds to the DNA binding site of nuclear factor-κB (NF-κB) p50 subunit, and surface plasmon resonance (SPR) analysis showed that PL binds to p50 concentration-dependently. Moreover, co-treatment of PL with NF-κB inhibitor phenylarsine oxide (0.1 μM) or p50 siRNA (100 nM) augmented PL-induced inhibitory effect on cell growth and activation of Fas and DR4. Notably, co-treatment of PL with p50 mutant plasmid (C62S) partially abolished PL-induced cell growth inhibition and decreased the enhanced expression of Fas and DR4. In xenograft mice model, PL (2.5–5 mg/kg) suppressed tumor growth of NSCLC dose-dependently. Therefore, these results indicated that PL could inhibit lung cancer cell growth via inhibition of NF-κB signaling pathway in vitro and in vivo.

Discovery of piperlongumine as a potential novel lead for the development of senolytic agents

“…PL modulates the activity of many cell signaling and survival pathways in cancer cells [31], and a number of studies have investigated the MOA by which PL induces apoptosis in these cells [30, 35–40, 45, 54–69]. Data from these studies may be translatable to PL-induced SC apoptosis because SCs and cancer cells share some common pro-survival pathways [23].…”

Novel piplartine-containing ruthenium complexes: synthesis, cell growth inhibition, apoptosis induction and ROS production on HCT116 cells

“…Piplartine was shown to reduce the number of viable cells and induces cell apoptosis on HCT116 cells by JNK signaling pathway [ 23 ], and induces apoptosis and autophagy through modulation of the PI3K/Akt/mTOR pathway in human lung cancer cells [ 22 ]. It can also induce apoptotic cell death and suppress the DNA binding activity of NF-κB in a concentration-dependent manner in non-small cell lung cancer cells [ 15 ]. The ruthenium complexes can also induce apoptosis of cancer cells through pathways mediated by death receptor, mitochondria and/or endoplasmic reticulum stress.…”

“…NFKBIA (NF-κB inhibitor alpha) gene encodes a member of NF-κB inhibitor family. As mentioned above, piplartine can lead to apoptotic cell death by NF-κB inhibition in non-small cell lung cancer cells [ 15 ]. The TP53 (tumor protein p53) gene encodes a tumor suppressor protein.…”

“…Later, the anticancer potential of piplartine and its analogs, alone or in combination, including combination with paclitaxel, cisplatin, gemcitabine and curcumin, have been extensively explored [ 10 , 16 , 19 – 21 ]. These studies reported the ability of piplartine to induce apoptosis and/or autophagy through modulation of the PI3K/Akt/mTOR, NF-κB, JAK1,2/STAT3 and/or JNK pathways in cancer cells [ 14 , 15 , 22 – 24 ]. In addition, piplartine is a direct TrxR1 inhibitor and can inhibit cell migration/invasion via ROS/ER/MAPKs/CHOP axis [ 25 , 26 ].…”

Leishmanicidal Effects of Piperlongumine (Piplartine) and Its Putative Metabolites

“…), and Piper arborescens Roxb. PPL has shown a broad spectrum of biological activities [11][12][13][14], including several tumor cell lines with minimal to no impact in normal cells [14]. In addition, PPL has demonstrated promising activity towards parasite species that cause neglected tropical diseases [15][16][17][18].…”