title: TW01001, a novel piperazinedione compound, induces mitotic arrest and autophagy in non-small cell lung cancer A549 cells.
abstract: Here, we report that TW01001, a novel piperazinedione compound, could be a new mitotic inhibitor for the treatment of non-small cell lung cancer by the following observations in A549 cells: (1) induction of cells to accumulate at G2/M phase, which ultimately led to cell apoptotic death, (2) accumulation of p53 and inhibition of survival signalings, and (3) induction of p53-independent autophagy. Taken together, our data suggested that TW01001 induces autophagy-p53-signaling pathway to cause mitotic arrest and cell growth inhibition in A549 cells and provides the framework for further development as a novel therapeutic agent for lung cancer treatment.
authors.affiliation: Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Mei-Chuan
authors.initials: MC
authors.lastname: Chen
authors.forename: Chun-Han
authors.initials: CH
authors.lastname: Chen
authors.forename: Yi-Nan
authors.initials: YN
authors.lastname: Liu
authors.forename: Hui-Po
authors.initials: HP
authors.lastname: Wang
authors.forename: Shiow-Lin
authors.initials: SL
authors.lastname: Pan
authors.forename: Che-Ming
authors.initials: CM
authors.lastname: Teng
mesh_terms: D001343:Autophagy / Q000187:drug effects; D001565:Benzoates / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D054659:Diketopiperazines / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008938:Mitosis / Q000187:drug effects*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction
chemical_list: C586098:3-((6-((5-benzylidene-3,6-dioxopiperazin-2-ylidene)methyl)pyridin-3-yloxy)methyl)benzoic acid; D001565:Benzoates; D054659:Diketopiperazines; D010879:Piperazines; C003905:3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione