Naftopidil is useful for the treatment of malignant pleural mesothelioma

Our plain-English summary of Naftopidil is useful for the treatment of malignant pleural mesothelioma, by K. Mikami, H. Nagaya, A. Gotoh, et al (Pharmacology, 2014).

The study

• Authors: K. Mikami, H. Nagaya, A. Gotoh, T. Kanno, A. Tsuchiya, T. Nakano, T. Nishizaki
• Journal: Pharmacology
• Published: 2014;94(3-4):163-9
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

© 2014 S. Karger AG, Basel.

In plain English

This was a laboratory study, not a study of patients. The authors tested naftopidil, a drug developed for benign prostate enlargement and high blood pressure, on a commercially obtained human malignant pleural mesothelioma cell line called NCI-H2052, and on male nude mice that had these cells injected under the skin. In dishes, naftopidil reduced cell survival as the concentration rose from 1 to 100 μmol/l, reaching almost 0% of normal levels at 100 μmol/l. It also significantly increased the share of cells showing signs of programmed cell death (apoptosis). It activated the enzymes caspase-3 and caspase-8, markedly raised TNF-α gene activity, and increased the release of a protein called FasL from the cells. In mice given naftopidil at 9.8 mg/kg twice a week, tumor growth was significantly lower than in control mice (p less than 0.001). All treated mice survived 8 weeks after the first injection, and the drug had no effect on their body weight. The authors concluded that naftopidil may have promising characteristics to be developed as a drug for treating malignant pleural mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study using a human mesothelioma cell line in culture, plus an animal experiment in mice carrying tumors grown from that cell line
• Who was studied: NCI-H2052 human malignant pleural mesothelioma cells (from the American Type Culture Collection), and male 6-week-old nude BALB/c-nu/nu mice given 1 × 10^7 of these cells under the skin of the right flank. The tumor-volume figure reports n = 6, but the article does not clearly state the number of mice.
• Exposure: No asbestos exposure was studied. The exposure was the drug naftopidil, an alpha-1 adrenoceptor blocker: 1 to 100 μmol/l in cell experiments (mostly 100 μmol/l), and 9.8 mg/kg injected into the abdominal cavity twice a week in mice, starting 1 week after the cells were injected. Control mice received a physiological salt solution.
• Main results:
  • In NCI-H2052 cells, naftopidil reduced cell viability in a concentration-dependent manner (1 to 100 μmol/l, 24 h), reaching almost 0% of basal levels at 100 μmol/l
  • Naftopidil (100 μmol/l for 12 h) significantly increased the number of TUNEL-positive (apoptotic) cells compared with untreated control cells
  • In NCI-H2052 cells, naftopidil activated caspase-3 and caspase-8; the article reports that caspase-9 was not activated
  • Naftopidil (100 μmol/l) markedly upregulated TNF-α mRNA in NCI-H2052 cells. DR5 and DR6 mRNAs were slightly upregulated, and the other death-receptor-related mRNAs tested showed no significant change.
  • Naftopidil did not change FasL protein inside the cells, but significantly increased FasL in the surrounding culture medium, with a peak at 6 h
  • In mice with NCI-H2052 tumors, naftopidil significantly inhibited tumor growth compared with control mice (p < 0.001, Fisher's PLSD test)
  • All naftopidil-treated mice survived 8 weeks after the first injection, and naftopidil had no effect on mouse body weight
• The authors' conclusion: The authors concluded that naftopidil induces apoptosis of NCI-H2052 mesothelioma cells and suppresses the growth of tumors from these cells in mice, and that it may have promising characteristics to be developed as a drug for treating malignant pleural mesothelioma

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Apoptosis, Necrosis.

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