Sn- and Ge- triorganometallics exert different cytotoxicity and modulation of migration in triple-negative breast cancer cell line MDA-MB-231

Toxicol Lett. 2017 Sep 5:279:16-21. doi: 10.1016/j.toxlet.2017.07.879. Epub 2017 Jul 12.

Abstract

Among a variety of metal containing organic compounds, tin derivatives are enjoying an increasing interest and appear to be very promising as potential drug candidates. We studied eight organometallic derivatives, nuclear retinoid X receptor (RXR) ligands and two germanium containing derivates that do not serve as RXR ligands. Tributylgermanium chloride (TBGe) and triphenylgermanium chloride (TPGe) did not inhibit growth of human triple negative MDA-MB-231 breast cancer cells. On the other hand, the tributyltin derivatives were highly, the triphenyltin derivatives less cytotoxic, both groups with IC50 values of nanomolar range. All trialkyltin derivatives (tributyltin chloride, tributyltin bromide, tributyltin iodide, tributyltin hydride) and three triaryltin derivatives (triphenyltin chloride, triphenyltin hydride and triphenyltin hydroxide) caused caspase-3/7 dependent apoptosis. Those derivatives that showed no or weak cytotoxicity, TBGe, TPGe, and triphenyltin acetate, we found to reduce migration of tested triple negative breast cancer cells.

Keywords: Apoptosis; Cytotoxicity; Nuclear retinoid x receptor; Triorganotin/triorganogermanium derivatives; Triple negative breast cancer.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Neoplasm Invasiveness
  • Organometallic Compounds / pharmacology*
  • Organotin Compounds / pharmacology*
  • Retinoid X Receptors / drug effects
  • Retinoid X Receptors / metabolism
  • Signal Transduction / drug effects
  • Time Factors
  • Trialkyltin Compounds / pharmacology
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Organotin Compounds
  • Retinoid X Receptors
  • Trialkyltin Compounds
  • germanium chloride
  • tributyltin
  • triphenyltin
  • CASP3 protein, human
  • CASP7 protein, human
  • Caspase 3
  • Caspase 7