Topoisomerase I inhibitor SN-38 effectively attenuates growth of human non-small cell lung cancer cell lines in vitro and in vivo

J Environ Pathol Toxicol Oncol. 2011;30(1):1-10. doi: 10.1615/jenvironpatholtoxicoloncol.v30.i1.10.

Abstract

The effect of SN-38 was evaluated on multiple lung cancer cell lines. It inhibits anchorage-dependent and -independent growth as monitored by MTT and soft agar colony assay, respectively. SN-38 collapsed the mitochondrial membrane potential (MMP), arrested cells in S- and G2-phases of the cell cycle, and induced apoptosis via activation of caspase 3 and PARP. A single injection of 2 mg/kg body weight of SN-38 caused a significant reduction of lung cancer xenografts. These findings indicate that SN-38 induces apoptosis in the lung cancer cells effectively. Thus, SN-38 can potentially be an effective therapeutic agent against lung cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Apoptosis / drug effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology
  • Carcinoma, Lewis Lung / drug therapy
  • Carcinoma, Lewis Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Caspase 3 / physiology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Irinotecan
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Poly(ADP-ribose) Polymerases / physiology
  • Topoisomerase I Inhibitors / pharmacology*

Substances

  • Antineoplastic Agents, Alkylating
  • Topoisomerase I Inhibitors
  • Irinotecan
  • Poly(ADP-ribose) Polymerases
  • Caspase 3
  • Camptothecin