ISSN:
1600-0625
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Capsaicin has been shown the different biologic and toxic effects on the non-neuronal celIs and serveral transformed cells. The present study aimed at evaluating the cytotoxic mechanism of capsacin on the cultured human skin fibroblast. Normal neonatal human fibroblasts were used for MTT assay to measure the changes of celI survival, while growth factors, receptor antagonist, antioxidants and calcium modulators were pretreated or co-treated with capsaicin. Fibroblast survival was significantly stimulated with EGF (10 ng/ml), bFGF (10 ng/ml) and capsazepine (10 µm) but inhibited by cycloheximide (1 µg/ml). When 200 µm capsaicin is given to fibroblasts, chromatin condensations were observed at 12 h, and cell survival rate was reduced to 25–50% at 24 h. Vanilloid receptor antagonists, capsazepine and ruthenium red did not prevent the toxic effect of capsaicin, and 10 µm capsazepine rather paradoxically enhanced the cytotoxicity. In contrast to bFGF (10 ng/ml), EGF (10, 100 ng/ml) enhanced the cytotoxicity of capsaicin. Neuropeptides, substance P (1, 10 nm) and CGRP (1, 10 nm), and a structural analogue to capsaicin, tyrosine (0.3–1.2 mm) did not affect the cytotoxicity. However, antioxidants trolox (100 µm) and ascorbic acid (0.1, 0.3 mm) reduced the capsaicin cytotoxicity. Of calcium-modulating agents, nifedifine, a Ca2+ channel blocker (10, 20 µm) and cyclopiazonic acid, a Ca2+-ATPase inhibitor in ER (10 µm) did not influence the cytotoxicity, but BAPTA/AM as a chelater for cytoplasmic free calcium ion (10 µm) significantly decreased capsaicin cytotoxicity. Unlike cycloheximide, a protein synthesis inhibitor, z-VAD-FMK, a non-specific caspase inhibitor, prevented the capsaicin cytotoxicity. The DNA ladder and TUNEL-positive cells were observed from the capsaicin-treated fibroblasts and Western blot revealed caspase-3 activity. Thus, capsaicin-induced cytotoxicity on human skin fibroblasts is more likely to suggest the mechanism of apoptotic pathway where antioxidants may play a role to prevent it.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.0906-6705.2004.0212cd.x
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