Korean J Dermatol.  2005 Feb;43(2):194-203.

Cytotoxicity of Capsaicin on Cultured Human Skin Fibroblast

Affiliations
  • 1Department of Dermatology, Chonbuk National University, Korea.
  • 2Department of Pharmacology, Chonnam National University, Gwangju, Korea.
  • 3Department of Dermatology, Chonnam National University, Gwangju, Korea. yhwon@chonnam.ac.kr

Abstract

BACKGROUND
Capsaicin has been shown to have different biologic and toxic effects, depending on non-neuronal cells and several transformed cells, however no study has been reported from cultured human skin fibroblast. OBJECTIVE: Present study was aimed to evaluate the cytotoxicity and its mechanism of capsacin on the cultured human skin fibroblast. MATERIAL AND METHOD: Normal neonatal human fibroblasts were used, and changes of cell survival were measured by MTT assay after the cells were pre-treated with growth factors, receptor antagonist, antioxidants, calcium modulators were pre-treated or co-treated with capsaicin. RESULTS: Suvival of fibroblast was significantly increased by treatment with EGF (10ng/ml), bFGF (10ng/ml), capsazepine (10M) but inhibited by cycloheximide (1g/ml). When 200 M capsaicin was added to fibroblasts, chromatin condensations were observed at 12 hours and cell survival rate was reduced to 25-50% at 24 hours. Vanilloid receptor antagonists, capsazepine and ruthenium red, did not prevent the toxic effect of capsaicin, and 10M capsazepine paradoxically rather enhanced the cytotoxicity. In contrast to bFGF (10ng/ml), EGF (10, 100ng/ml) enhanced the cytotoxicity of capsaicin. Neuropeptides, substance P (1, 10nM) and CGRP (1, 10nM), and a structural analogue to capsaicin, tyrosine (0.3-1.2mM) did not affect the cytotoxicity. However, antioxidants such as trolox (100M) and ascorbic acid (0.1, 0.3 mM) reduced the capsaicin cytotoxicity. Of calcium modulating agents, nifedifine, a Ca2+ channel blocker (10, 20M) and cyclopiazonic acid, a Ca2+-ATPase inhibitor in ER (10M) did not influence the cytotoxicity, however BAPTA/AM (10M) as a chelater for cytoplasmic free calcium ion (10M) significantly decreased capsaicin cytotoxicity. Unlike cycloheximide, z-VAD-FMK, a protein synthesis inhibitor and a non-specific caspase inhibitor, prevented the capsaicin cytotoxicity. The DNA ladder and TUNEL positive cells were observed among the capsaicin treated fibroblasts and Western blot revealed caspase-3 activity. CONCLUSION: The capsaicin-induced cytotoxicity on human skin fibroblasts is likely to suggest the mechanism of an apoptotic pathway, which can possibly be prevented by antioxidants.

Keyword

Capsaicin; Cytotoxicity; Fibroblast

MeSH Terms

Antioxidants
Ascorbic Acid
Blotting, Western
Calcium
Capsaicin*
Caspase 3
Cell Survival
Chromatin
Cycloheximide
Cytoplasm
DNA
Epidermal Growth Factor
Fibroblasts*
Humans*
In Situ Nick-End Labeling
Intercellular Signaling Peptides and Proteins
Neuropeptides
Ruthenium Red
Skin*
Substance P
Tyrosine
Antioxidants
Ascorbic Acid
Calcium
Capsaicin
Caspase 3
Chromatin
Cycloheximide
DNA
Epidermal Growth Factor
Intercellular Signaling Peptides and Proteins
Neuropeptides
Ruthenium Red
Substance P
Tyrosine
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