Naftopidil is useful for the treatment of malignant pleural mesothelioma.

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.

• Authors: Koji Mikami, Hisao Nagaya, Akinobu Gotoh, Takeshi Kanno, Ayako Tsuchiya, Takashi Nakano, Tomoyuki Nishizaki
• Journal: Pharmacology (Pharmacology) Vol. 94 Issue 3-4 Pg. 163-9 ( 2014) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 25301502 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• 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

Topics

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