Synthesis, structural characterization, and anticancer activity of a monobenzyltin compound against MCF-7 breast cancer cells

Drug Des Devel Ther. 2015 Nov 23:9:6191-201. doi: 10.2147/DDDT.S87064. eCollection 2015.

Abstract

A new monoorganotin Schiff base compound, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, (compound C1), was synthesized, and its structural features were investigated by spectroscopic techniques and single-crystal X-ray diffractometry. Compound C1 was exposed to several human cancer cell lines, including breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, ovarian adenocarcinoma cell lines Skov3 and Caov3, and prostate cancer cell line PC3, in order to examine its cytotoxic effect for different forms of cancer. Human hepatic cell line WRL-68 was used as a normal cell line. We concentrated on the MCF-7 cell line to detect possible underlying mechanism involvement of compound C1. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed the strongest cytotoxicity of compound C1 against MCF-7 cells, with a half maximal inhibitory concentration (IC50) value of 2.5±0.50 μg/mL after 48 hours treatment. The IC50 value was >30 μg/mL in WRL-68 cells. Induced antiproliferative activity of compound C1 for MCF-7 cells was further confirmed by lactate dehydrogenase, reactive oxygen species, acridine orange/propidium iodide staining, and DNA fragmentation assays. A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis. Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment. Morphological changes of necrosis and early and late apoptosis stages were observed in treated cells after staining with acridine orange/propidium iodide. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Results of the present study obviously reveal potential cytotoxic effects of compound C1 against human breast cancer MCF-7 cells.

Keywords: MCF-7 cells; apoptosis; organotin derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • DNA Fragmentation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • MCF-7 Cells
  • Models, Molecular
  • Molecular Structure
  • Organotin Compounds / chemical synthesis
  • Organotin Compounds / chemistry
  • Organotin Compounds / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Schiff Bases / chemical synthesis
  • Schiff Bases / chemistry
  • Schiff Bases / pharmacology*
  • Structure-Activity Relationship

Substances

  • (N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato)(o-methylbenzyl)aquatin(IV)
  • Antineoplastic Agents
  • Organotin Compounds
  • Reactive Oxygen Species
  • Schiff Bases
  • L-Lactate Dehydrogenase