The Effects of Verapamil on Growth and Apoptosis of Keloid Fibroblast.

Park, Jung Min; Lee, Keun cheol; Kim, Seok Kwun; Bae, Hae Rahn; Rha, Seo Hee

Original Article

Journal of the Korean Society of Plastic and Reconstructive Surgeons 2005;32(5):625-634.
Published online September 1, 2005.

The Effects of Verapamil on Growth and Apoptosis of Keloid Fibroblast.

Jung Min Park, Keun cheol Lee, Seok Kwun Kim, Hae Rahn Bae, Seo Hee Rha

¹Department of Plastic & Reconstructive Surgery, College of Medicine, Dong-A University, Busan, Korea. jmpark@daunet.donga.ac.kr
²Department of Physiolog, College of Medicine, Dong-A University, Busan, Korea.
³Department of Pathology, College of Medicine, Dong-A University, Busan, Korea.

Abstract

In this study, the effects of verapamil on growth rate, apoptosis, production of transforming growth factor (TGF-beta) and fibronectin were evaluated in keloid and normal human dermal fibroblasts. Both fibroblasts were primarily cultured from earlobe keloids of three female patients and treated with various concentrations of verapamil. Cell toxicity was assessed by MTT assay, growth rate and apoptosis by FACS, and the production of TGF-beta and fibronectin by ELISA and Western blot, respectively. In the MTT50, the cell growth was more suppressed in keloid fibroblasts. In the MTT90, cell growth was more stimulated in normal fibroblasts. No significant effect appeared on TGF-beta expression but an increase in extracellular fibronectin secretion was found in keloid fibroblasts. Keloid fibroblasts responded to verapamil more sensitively, and the percentage of apoptosis was higher at the MTT50l. In brief, verapamil had growth-inhibitory effect with inducing apoptosis at the MTT50, but rather growth-stimulatory effect at the MTT90. The biphasic effect of verapamil depending on the dose might explain one of the reasons of relapse after keloid treatment with verapamil. Clinical application with high concentration (2.5mg/ml) is advised unless excessive dosage is used.

Keywords: Keloid; Verapamil