TW01001, a novel piperazinedione compound, induces mitotic arrest and autophagy in non-small cell lung cancer A549 cells

Cancer Lett. 2013 Aug 19;336(2):370-8. doi: 10.1016/j.canlet.2013.03.028. Epub 2013 Apr 6.

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.

MeSH terms

  • Autophagy / drug effects
  • Benzoates / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle Checkpoints / drug effects
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Diketopiperazines / pharmacology*
  • G2 Phase / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mitosis / drug effects*
  • Piperazines / administration & dosage
  • Piperazines / pharmacology
  • Piperazines / therapeutic use*
  • Signal Transduction

Substances

  • 3-((6-((5-benzylidene-3,6-dioxopiperazin-2-ylidene)methyl)pyridin-3-yloxy)methyl)benzoic acid
  • Benzoates
  • Diketopiperazines
  • Piperazines
  • 3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione