Inducible nitric oxide inhibitor enhances the anti-tumor effect of cisplatin on CNE-2 cells by inducing cell apoptosis

Eur Rev Med Pharmacol Sci. 2014 Oct;18(19):2789-97.

Abstract

Objective: Inducible nitric oxide (NO) synthase (iNOS) inhibitor S-methylisothiourea (SMT) has been reported to have anti-tumor effects on several types of cancers. We aimed to investigate whether SMT can inhibit nasopharyngeal carcinoma cells CNE-2 proliferation through raise chemotherapy effect of diaminodichloroplatinum (DDP).

Materials and methods: CNE-2 cells were treated with SMT, DDP and both of them respectively. MTT and colony-forming assay was performed to detect the proliferation effect of the treatment. Hoechst 33258 staining and apoptosis analysis were performed to investigate the apoptosis effect of chemotherapy. Additionally, the NO level was detected to estimate the activity of iNOS.

Results: CNE-2 cells expressed high level of iNOS. SMT can inhibit CNE-2 cells growth in a dose-dependent manner and have the effect on reducing dosage of DDP as well as enhancing the anti-tumor efficacy by promote cell apoptosis.

Conclusions: Our findings suggested that SMT play a synergism role in the inhibition process of DDP on nasopharyngeal carcinoma, and SMT could be a promising therapeutic factor for cancer prevention.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects*
  • Carcinoma
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Humans
  • Isothiuronium / analogs & derivatives*
  • Isothiuronium / pharmacology
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / enzymology
  • Nasopharyngeal Neoplasms / pathology
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*

Substances

  • Isothiuronium
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • S-methylisothiopseudouronium
  • Cisplatin