title: 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.
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Dong Ju
authors.initials: DJ
authors.lastname: Son
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Gu
authors.affiliation: New Drug Development Center, KBio, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Ju Rang
authors.initials: JR
authors.lastname: Woo
authors.affiliation: Department of Chemistry, Utah Valley University, 800 West University Parkway, Orem, UT 84508, USA.
authors.forename: Young Wan
authors.initials: YW
authors.lastname: Ham
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Hee Pom
authors.initials: HP
authors.lastname: Lee
authors.affiliation: College of Medicine, Chungbuk National University, Chungdae-ro 1, Seowon-gu, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Wun Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Jung
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Osong-eup, Heungduk-gu, Cheongju, Chungbuk 28160, Republic of Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004148:Dioxolanes / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D010881:Piperidones
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004148:Dioxolanes; D016328:NF-kappa B; C498077:piperlongumine; D010881:Piperidones