Tocotrienol inhibits proliferation of human Tenon's fibroblasts in vitro: a comparative study with vitamin E forms and mitomycin C.

Abstract

PURPOSE:

To evaluate the potential of the vitamin E compound alpha-tocotrienol as antifibrotic agent in vitro.

METHODS:

Using human Tenon's capsule fibroblast cultures, the antiproliferative and cytotoxic effects of the different vitamin E forms alpha-tocopherol, alpha-tocopheryl acetate, alpha-tocopheryl succinate and alpha-tocotrienol were compared with those of mitomycin C. To mimic subconjunctival and regular oral application in vivo, exposure time of serum-stimulated and serum-restimulated fibroblasts (SF and RF, respectively) to vitamin E forms was set at 6 days. Cultures were only exposed for 5 min to mitomycin C due to its known acute toxicity and to mimic the short-time intraoperative administration. Proliferation (expressed as % of control) was determined by DNA content quantification on days 2, 4 and 6, whereas cytotoxicity was assessed by cell morphology and glucose 6-phosphate dehydrogenase (G6PD) release after 24 h.

RESULTS:

alpha-Tocopherol and alpha-tocopheryl acetate stimulated growth of SF, but not RF. Reduction of fibroblast content by alpha-tocopheryl succinate was accompanied by increased G6PD release and necrosis. Contrary to alpha-tocopheryl succinate, 50 microM or repeatedly 20 microM of alpha-tocotrienol significantly inhibited proliferation without causing cellular toxicity (maximal effect: 46.8%). RF were more sensitive to this effect than SF. Mitomycin C 100-400 microg/ml showed a stronger antiproliferative effect than alpha-tocotrienol (maximal effect: 13.8%). Morphologic characteristics of apoptosis were more commonly found under treatment with mitomycin C.

CONCLUSIONS:

Of the vitamin E forms tested, only alpha-tocotrienol significantly inhibited growth at non-toxic concentrations. In this in vitro study, antiproliferative effects of mitomycin C were stronger than those of alpha-tocotrienol.

• Authors: Alexander Meyenberg, David Goldblum, Jean-Marc Zingg, Angelo Azzi, Kalanithi Nesaretnam, Monika Kilchenmann, Beatrice E Frueh
• Journal: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie (Graefes Arch Clin Exp Ophthalmol) Vol. 243 Issue 12 Pg. 1263-71 (Dec 2005) ISSN: 0721-832X [Print] Germany
• PMID: 15909162 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antioxidants
• Nucleic Acid Synthesis Inhibitors
• Tocotrienols
• Vitamin E
• Mitomycin
• DNA
• Glucosephosphate Dehydrogenase

Topics

• Aged
• Aged, 80 and over
• Antioxidants (pharmacology)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Conjunctiva (drug effects, metabolism, pathology)
• Cytoplasm (drug effects, enzymology)
• DNA (analysis)
• Fibroblasts (drug effects, metabolism, pathology)
• Glucosephosphate Dehydrogenase (drug effects, metabolism)
• Humans
• In Vitro Techniques
• Mitomycin (pharmacology)
• Nucleic Acid Synthesis Inhibitors (pharmacology)
• Tocotrienols (pharmacology)
• Vitamin E (pharmacology)