Selective anticancer activity of the novel steroidal dihydropyridine spirooxindoles against human esophageal EC109 cells

Biomed Pharmacother. 2017 Dec:96:1186-1192. doi: 10.1016/j.biopha.2017.11.100. Epub 2017 Nov 28.

Abstract

A series of small-molecule compounds built on steroidal dihydropyridine spirooxindoles has been reported previously. In this study, the compound 5l showed strong anti-cancer activity, especially in the esophageal cancer. Three esophageal squamous cell lines and paclitaxel-resistant cell line were investigated. The results demonstrated that compound 5l was most efficient in the EC109 cells, induced cell apoptosis through elevation of cellular ROS levels, caused G2/M phase arrest and mitochondrial dysfunction. Further study confirmed that the mechanism of 5l in esophageal cancer treatment was related to the Bcl-2 family and caspase receptor-mediated apoptotic pathway.

Keywords: Antiproliferative activity; Esophageal cancer; Mechanistic studies; Steroidal dimmer.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Dihydropyridines / pharmacology*
  • Drug Resistance / drug effects
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Paclitaxel / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Small Molecule Libraries / pharmacology

Substances

  • Antineoplastic Agents, Phytogenic
  • Dihydropyridines
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Small Molecule Libraries
  • 1,4-dihydropyridine
  • Paclitaxel