Discovery of indoline derivatives that inhibit esophageal squamous cell carcinoma growth by Noxa mediated apoptosis

Bioorg Chem. 2019 Nov:92:103190. doi: 10.1016/j.bioorg.2019.103190. Epub 2019 Aug 10.

Abstract

A series of novel indoline derivatives were synthesized and evaluated for antiproliferative activity against four selected cancer cell lines (Hela, A549, HepG2 and KYSE30). Among them, compound 20 displayed the potent inhibition activity against esophageal cancer cells (Kyse30, Kyse450, Kyse510 and EC109). Cellular mechanism studies in esophageal squamous cell carcinoma (ESCC) cells elucidated compound 20 inhibited cell growths in vitro and in vivo, reduced colony formation, arrested cell cycle at M phase, and induced Noxa-dependent apoptosis in ESCC. Importantly, compound 20 was identified as a novel Noxa mediated apoptosis inducer. These results suggested that compound 20 might be a promising anticancer agent with potential for development of further clinical applications.

Keywords: Cell growths in vitro and in vivo; Esophageal squamous cell carcinoma; Indoline; Noxa-dependent apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Squamous Cell Carcinoma / drug therapy*
  • Humans
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Molecular Structure
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Small Interfering / metabolism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Indoles
  • PMAIP1 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • indoline