Sensitization of non-small cell lung cancer cells to cisplatin by naturally occurring isothiocyanates

Chem Res Toxicol. 2010 Aug 16;23(8):1307-9. doi: 10.1021/tx100187f.

Abstract

We show that naturally occurring isothiocyanates (ITCs) sensitize human non-small cell lung cancer cells to cisplatin. Moreover, the structure of the ITC side chain moiety is important for sensitization. In NCI-H596 cells, 20 microM benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC) enhance the efficacy of various concentrations of cisplatin, but sulforaphane (SFN) does not. Reducing the concentration of BITC and PEITC to 10 microM still allows for the sensitization of cells to cisplatin. Neither cellular platinum accumulation nor DNA platination account for this increased cytotoxicity. BITC and PEITC deplete beta-tubulin, but SFN does not; this correlates with and may be important for sensitization.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / chemistry
  • Cisplatin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Isothiocyanates / chemistry
  • Isothiocyanates / pharmacology*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Molecular Structure
  • Sensitivity and Specificity

Substances

  • Antineoplastic Agents
  • Isothiocyanates
  • Cisplatin