Autophagy Induced by Naftopidil Inhibits Apoptosis of Human Gastric Cancer Cells

Anticancer Res. 2018 Feb;38(2):803-809. doi: 10.21873/anticanres.12287.

Abstract

Aim: Naftopidil is used to treat benign prostate hyperplasia. Moreover, previous studies have shown that naftopidil reduced viability of many types of cancer cells. Therefore, we investigated the antitumor mechanism of naftopidil in this study.

Materials and methods: We used the HGC27 human gastric cancer cell line. It was treated with naftopidil, pan-caspase inhibitor, and chloroquine diphosphate (CQ). Cell viability and cell death were investigated by the assay and annexin V/ propidium iodide assay. Phosphorylation of protein kinase B (AKT) (Ser473) was measured by western blotting. Alteration of light chain 3B (LC3B) was investigated by western blotting and immunofluorescence.

Results: Naftopidil reduced phospho-AKT (Ser473) and altered LC3B. Combination of naftopidil and CQ reduced cell viability and phospho-AKT (Ser 473).

Conclusion: Naftopidil induces apoptosis and autophagy of HGC27 cells, however, autophagy is considered to inhibit apoptosis. We concluded naftopidil and CQ have a synergistic antitumor effect.

Keywords: Naftopidil; apoptosis; autophagy; drug repositioning; gastric cancer.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Chloroquine / administration & dosage
  • Chloroquine / analogs & derivatives
  • Chloroquine / pharmacology
  • Drug Synergism
  • Humans
  • Microtubule-Associated Proteins / metabolism
  • Naphthalenes / administration & dosage
  • Naphthalenes / pharmacology*
  • Phosphorylation
  • Piperazines / administration & dosage
  • Piperazines / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology

Substances

  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • Naphthalenes
  • Piperazines
  • chloroquine diphosphate
  • Chloroquine
  • Proto-Oncogene Proteins c-akt
  • naftopidil