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Am J Physiol Cell Physiol 295: C931-C943, 2008. First published July 23, 2008; doi:10.1152/ajpcell.00266.2008
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VASCULAR BIOLOGY

In vitro and in vivo wound healing-promoting activities of β-lapachone

Hsiu-Ni Kung,1 Mei-Jun Yang,1 Chi-Fen Chang,1 Yat-Pang Chau,2,* and Kuo-Shyan Lu1,*

1Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University; and 2Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan

Submitted 21 May 2008 ; accepted in final form 17 July 2008

Impaired wound healing is a serious problem for diabetic patients. Wound healing is a complex process that requires the cooperation of many cell types, including keratinocytes, fibroblasts, endothelial cells, and macrophages. β-Lapachone, a natural compound extracted from the bark of the lapacho tree (Tabebuia avellanedae), is well known for its antitumor, antiinflammatory, and antineoplastic effects at different concentrations and conditions, but its effects on wound healing have not been studied. The purpose of the present study was to investigate the effects of β-lapachone on wound healing and its underlying mechanism. In the present study, we demonstrated that a low dose of β-lapachone enhanced the proliferation in several cells, facilitated the migration of mouse 3T3 fibroblasts and human endothelial EAhy926 cells through different MAPK signaling pathways, and accelerated scrape-wound healing in vitro. Application of ointment with or without β-lapachone to a punched wound in normal and diabetic (db/db) mice showed that the healing process was faster in β-lapachone-treated animals than in those treated with vehicle only. In addition, β-lapachone induced macrophages to release VEGF and EGF, which are beneficial for growth of many cells. Our results showed that β-lapachone can increase cell proliferation, including keratinocytes, fibroblasts, and endothelial cells, and migration of fibroblasts and endothelial cells and thus accelerate wound healing. Therefore, we suggest that β-lapachone may have potential for therapeutic use for wound healing.

cell proliferation; mitogen-activated protein kinase signaling pathways


Addresses for reprint requests and other correspondence: K.-S. Lu, Dept. of Anatomy and Cell Biology, College of Medicine, National Taiwan Univ., No. 1, Sec. 1, Jen Ai Rd., Taipei, 100, Taiwan; Y.-P. Chau, Inst. of Anatomy and Cell Biology, School of Medicine, National Yang-Ming Univ., 155, Sec. 2, Li-Nung St., Shih-Pai, Taipei, 112, Taiwan (e-mail: lks{at}ntu.edu.tw; leonchau{at}ym.edu.tw)






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