Tohoku J. Exp. Med., 2009, 217(3)

Tranilast, an Anti-Allergic Drug, Down-Regulates the Growth of Cultured Neurofibroma Cells Derived from Neurofibromatosis Type 1

MISA YAMAMOTO,¹ TOSHIHIKO YAMAUCHI,² KOZUE OKANO,¹ MUTSUO TAKAHASHI,¹ SHOJI WATABE¹ and YOSHIMI YAMAMOTO³

¹Faculty of Health Sciences, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
²Department of Plastic Reconstructive Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan
³United Graduate School of Veterinary Science, Yamaguchi University, Ube, Yamaguchi, Japan

Neurofibromas are benign tumors that comprise primarily of Schwann cells and fibroblasts. Mast cells have been found scattered in the tumor tissue, and their role in promoting the proliferation of neurofibroma has been suggested. Tranilast (N-[3,4-dimethoxycinnamolyl]anthranilic acid) is an anti-allergic drug that inhibits release of the chemical mediators from mast cells and it used for the treatment of keloids and hypertrophic scars by its inhibition of growth-promoting transforming growth factor (TGF)-β₁ from fibroblasts. We assumed that tranilast would suppress neurofibroma cell growth. In order to prove this hypothesis, we investigated the effectiveness of tranilast in inhibiting the tumor growth using a new cell culture system obtained from patients with neurofibromas. We called this culture system with the mixture of Schwann cells and fibroblasts “NF1 cells culture”. Mast cells were differentiated from CD34⁺ peripheral blood mononuclear cells of normal healthy subjects, and were co-cultured with NF1 cells. Three days after tranilast (10 ∼ 100 μM) added to the culture dishes, we counted viable cell numbers and measured the concentrations of TGF-β₁, stem cell factor (SCF) and tryptase, which exists in the histamine granule, in the culture medium. Tranilast significantly suppressed proliferation of the NF1 cells and lowered the levels of TGF-β₁, SCF and tryptase. These results suggest that tranilast retards tumor proliferation through not only suppression of cell growth factor, but also the inhibition of a chemical mediator released from mast cells. Thus, tranilast can be a potent therapeutic agent to inhibit the growth of neurofibromas.

keywords —— tranilast; von Recklinghausen disease; neurofibroma; mast cell; co-culture.

© 2009 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2009, 217, 193-201

Correspondence: Misa Yamamoto, MT (Medical Technologist), CT (Cytologist), Faculty of Health Sciences, Yamaguchi University School of Medicine, Minami- Kogushi 1-1-1, Ube, Yamaguchi, 755-8554, Japan.

e-mail: yamamoms@yamaguchi-u.ac.jp