Naftopidil is useful for the treatment of malignant pleural mesothelioma

Pharmacology. 2014;94(3-4):163-9. doi: 10.1159/000368050. Epub 2014 Oct 4.

Abstract

Naftopidil, an α1-adrenoceptor blocker, induced apoptosis of human malignant pleural mesothelioma NCI-H2052 cells. Naftopidil upregulated the expression of tumor necrosis factor-α (TNF-α) mRNA in these cells. Naftopidil, alternatively, increased FasL secretion from NCI-H2052 cells, without affecting the expression of FasL mRNA and protein, and activated caspase-3 and -8 in NCI-H2052 cells. Naftopidil drastically suppressed tumor growth in mice inoculated with these cells. The results of the present study indicate that naftopidil induces apoptosis of NCI-H2052 cells by upregulating the expression of TNF-α and stimulating the secretion of FasL, a ligand for the death receptor Fas, both to activate caspase-8 and the effector caspase-3, leading to the suppression of NCI-H2052 cell proliferation in vivo. This raises the possibility that naftopidil could be developed as an effective drug for the treatment of malignant pleural mesothelioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Adrenergic alpha-Antagonists / therapeutic use*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / metabolism
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Mesothelioma / drug therapy*
  • Mesothelioma / pathology
  • Mesothelioma, Malignant
  • Mice, Nude
  • Naphthalenes / pharmacology
  • Naphthalenes / therapeutic use*
  • Piperazines / pharmacology
  • Piperazines / therapeutic use*
  • RNA, Messenger / metabolism
  • Tumor Burden / drug effects
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Adrenergic alpha-Antagonists
  • Antineoplastic Agents
  • Fas Ligand Protein
  • Naphthalenes
  • Piperazines
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • naftopidil