A potent indolylquinoline alleviates growth of human lung cancer cell tumorspheres

Apoptosis. 2017 Oct;22(10):1235-1245. doi: 10.1007/s10495-017-1401-3.

Abstract

To fight cancer at its roots by targeting cancer stem cells is a promising approach for therapy. Previously, an indolylquinoline derivative, 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline (EMMQ), was reported effectively inhibiting the growth of lung cancer cells through impairment of cellular mitochondria functions. To address more on drug efficiency, the study further exploited if EMMQ can impede the propagation of tumorspheres stemmed from non-small cell lung cancer cells. EMMQ inhibited proliferation of spheroids in culture. In animal models, administration of the drug attenuated the spheroid tumorigenicity. The activated apoptosis alleviated growth of xenograft tumors in immune-deficient mice as established by the enriched tumorspheres. More evidence suggested that the reduced stemness of the spheroid tumors is attributed to apoptotic death. The findings supported that EMMQ is an eligible approach to eradicate the minor but tumorigenic lung cancer tumorspheres.

Keywords: Apoptosis; Cancer stem cells; Indolylquinoline; Non-small cell lung cancer cells; Xenograft tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • Carcinogenesis / drug effects*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Indoles / pharmacology*
  • Indoles / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Mitochondria / drug effects
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • Neoplastic Stem Cells / transplantation
  • Quinolines / pharmacology*
  • Quinolines / therapeutic use*
  • Tumor Stem Cell Assay

Substances

  • 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline
  • Antineoplastic Agents
  • Indoles
  • Quinolines