title: Cooperative down-regulation of ribosomal protein L10 and NF-κB signaling pathway is responsible for the anti-proliferative effects by DMAPT in pancreatic cancer cells.
abstract: Dimethylaminoparthenolide (DMAPT), a water-soluble analogue of natural product parthenolide, possesses anti-inflammatory and anti-tumor activities. Despite that the anti-inflammatory mechanism of DMAPT has been well studied, specific target(s) for DMPAT and its anti-tumor mechanism remain poorly understood. In this study, to assess the anti-proliferative effects of DMAPT in pancreatic cancer cell lines and exploit its anti-tumor mechanism, serial affinity chromatograph was implemented to probe potential targets for DMAPT, revealing that ribosomal protein L10 (RPL10) is a specific binding protein of DMAPT in PANC-1 cells. DMAPT could decrease the expression of RPL10 accompanying its anti-proliferative effects. Mechanistically, in both PANC-1 cells and MiaPaca-2 cells, reduced expression of RPL10 triggered by DMAPT binding decreased the expression of either p65 or IKKγ through the direct binding between RPL10 and p65 or IKKγ. Together, the present study strongly implies that RPL10 is a novel target with therapeutic potential for the treatment of pancreatic cancer.
authors.affiliation: State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, People's Republic of China.
authors.forename: Yuna
authors.initials: Y
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, People's Republic of China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D000080882:Ribosomal Protein L10; D012269:Ribosomal Proteins / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C524858:LC-1 compound; D016328:NF-kappa B; C000630686:RPL10 protein, human; D012269:Ribosomal Proteins; D012717:Sesquiterpenes
keywords: DMAPT; NF-κB pathway; RPL10; mechanism; pancreatic cancer