Tocotrienol inhibits proliferation of human tenon's fibroblasts in vitro: a comparative study with vitamin e forms and mitomycin c

Meyenberg, Alexander. and Goldblum, David. and Zingg, Jean-Marc. and Azzi, Angelo. and Nesaretnam, Kalanithi. and Kilchenmann, Monika. and Frueh, Beatrice E. (2005) Tocotrienol inhibits proliferation of human tenon's fibroblasts in vitro: a comparative study with vitamin e forms and mitomycin c. [Proceedings Paper]

Purpose: To evaluate the potential of the vitamin E compound a- 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 a- tocopherol, a-tocopheryl acetate, a-tocopheryl succinate and a-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 minutes 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 hours. Results: a-Tocopherol and a-tocopheryl acetate stimulated growth of SF, but not RF. Reduction of fibroblast content by a-tocopheryl succinate was accompanied by increased G6PD release and necrosis. Contrary to a- tocopheryl succinate, 50 µM or repeatedly 20 µM of a-tocotrienol significantly inhibited proliferation without causing cellular toxicity (maximal effect: 46.8%). RF were more sensitive to this effect than SF. 100 to 400 µg/ml of mitomycin C showed a stronger antiproliferative effect than a-tocotrienol (maximal effect: 13.8%). Morphologic characteristics of apoptosis were more commonly found under treatment with mitomycin C. Conclusions: Of the tested vitamin E forms, only a-tocotrienol significantly inhibited growth at nontoxic concentrations. In this in vitro study, antiproliferative effects of mitomycin C were stronger, compared to a- tocotrienol.

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Abstract

Purpose: To evaluate the potential of the vitamin E compound a- 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 a- tocopherol, a-tocopheryl acetate, a-tocopheryl succinate and a-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 minutes 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 hours. Results: a-Tocopherol and a-tocopheryl acetate stimulated growth of SF, but not RF. Reduction of fibroblast content by a-tocopheryl succinate was accompanied by increased G6PD release and necrosis. Contrary to a- tocopheryl succinate, 50 µM or repeatedly 20 µM of a-tocotrienol significantly inhibited proliferation without causing cellular toxicity (maximal effect: 46.8%). RF were more sensitive to this effect than SF. 100 to 400 µg/ml of mitomycin C showed a stronger antiproliferative effect than a-tocotrienol (maximal effect: 13.8%). Morphologic characteristics of apoptosis were more commonly found under treatment with mitomycin C. Conclusions: Of the tested vitamin E forms, only a-tocotrienol significantly inhibited growth at nontoxic concentrations. In this in vitro study, antiproliferative effects of mitomycin C were stronger, compared to a- tocotrienol.

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Item Type:	Proceedings Paper
Additional Information:	Available at Perpustakaan Sultan Abdul Samad, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia. TP684 P3I61 2005 Call Number
AGROVOC Term:	tocotrienols
AGROVOC Term:	vitamin E
AGROVOC Term:	mitomycin
AGROVOC Term:	fibroblasts
AGROVOC Term:	analysis
AGROVOC Term:	statistical methods
AGROVOC Term:	chemical reagents
AGROVOC Term:	cell culture
AGROVOC Term:	cytotoxicity
AGROVOC Term:	disease prevention
Geographical Term:	Malaysia
Depositing User:	Nor Hasnita Abdul Samat
Date Deposited:	01 Nov 2025 08:22
Last Modified:	10 Nov 2025 01:04
URI:	http://webagris.upm.edu.my/id/eprint/1223

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