A thiopyran derivative with low murine toxicity with therapeutic potential on lung cancer acting through a NF-κB mediated apoptosis-to-pyroptosis switch

Apoptosis. 2019 Feb;24(1-2):74-82. doi: 10.1007/s10495-018-1499-y.

Abstract

Pyroptosis is a novel manner of cell death that can be mediated by chemotherapy drugs. The awareness of pyroptosis is significantly increasing in the fields of anti-tumor research and chemotherapy drugs. Invoking the occurrence of pyroptosis is an attractive prospect for the treatment of lung cancer. Here, the compound L61H10 was obtained as a thiopyran derivative to compare its activity with curcumin. It was indicated that L61H10 exhibited good anti-tumor activity both in vitro and in vivo via the switch of apoptosis-to-pyroptosis, which was associated with the NF-κB signaling pathway. In addition, L61H10 had no obvious side effects both in vitro and in vivo. In brief, L61H10 is shown to be a potential anti-lung cancer agent and research on its anti-tumor mechanism provides new information for chemotherapy drug research.

Keywords: Anti-lung cancer; Apoptosis; NF-κB; Pyroptosis; Toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • Pyrans / chemistry
  • Pyrans / pharmacology
  • Pyrans / therapeutic use*
  • Pyroptosis / drug effects*
  • Pyroptosis / physiology
  • RAW 264.7 Cells
  • Signal Transduction / drug effects
  • Sulfhydryl Compounds / chemistry*
  • Sulfhydryl Compounds / pharmacology
  • Sulfhydryl Compounds / therapeutic use
  • Toxicity Tests
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • NF-kappa B
  • Pyrans
  • Sulfhydryl Compounds
  • thiopyran