Piperlongumine analogue L50377 induces pyroptosis via ROS mediated NF-κB suppression in non-small-cell lung cancer

Chem Biol Interact. 2019 Nov 1:313:108820. doi: 10.1016/j.cbi.2019.108820. Epub 2019 Sep 10.

Abstract

Natural products with potent activity and less toxicity provide major sources for development of novel anti-cancer drugs. Herein, we evaluated the effects and the underlying mechanisms of a novel piperlongumine (PL) analogue L50377 on non-small-cell lung cancer (NSCLC) cells. The results revealed that L50377 displayed greater potentials of suppressing cell growth than PL. In addition, L50377 promoted cell apoptosis and pyroptosis via stimulating reactive oxygen species (ROS) generation in NSCLC cells. More interestingly, ROS mediated NF-κB suppression might be implicated in the mechanisms of L50377-induced pyroptosis in NSCLC cells. Taken together, our results suggested that L50377 served as a novel chemical agent might have great potentials for NSCLC treatment.

Keywords: Apoptosis; NF-κB; Non-small-cell lung cancer; Pyroptosis; ROS.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Dioxolanes / chemistry
  • Dioxolanes / pharmacology*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Pyroptosis / drug effects*
  • Reactive Oxygen Species / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Dioxolanes
  • NF-kappa B
  • Reactive Oxygen Species
  • piperlongumine