
Biotechnology and Applied Biochemistry (1999) 29, (213215) (Printed in Great Britain)
Effect of a-tocopherol andsilibin dihemisuccinate on the proliferation of human skinfibroblasts
D. Onat*, D. Boscoboinik, A. Azziand H. Basaga1
*Molecular Biology and Genetics Department, BogaziciUniversity, Bebek 80815 Istanbul, Turkey, Instituteof Biochemistry and Molecular Biology, University of Bern,Buhlstrasse 28 Postfach 3000 Bern 9, Switzerland, and Facultyof Engineering and Natural Sciences, Sabanc University, Bankalar Cad. No 2, 80020Karakoy, Istanbul, Turkey
Abbreviations used: SDH, silibin dihemisuccinate; PKC, protein
kinase C; FCS, fetal calf serum; ERK, extracellular
signal-regulated protein kinase.
1 To whom correspondence should be addressed.
Cell proliferation is a complex and important event in
atherosclerosis, aging and cancer, and is under the control of
signalling pathways. These signalling pathways in turn are
effected by the presence of a number of chemicals. For this
purpose, we have checked the effect of two chemicals on the
proliferation of skin fibroblasts. a-Tocopherol
and silibin dihemisuccinate (SDH) negatively regulate
proliferation of human skin fibroblasts. To check the cell-cycle
time intervals, a [3H]thymidine incorporation assay
was performed, showing DNA replication at around 24 h; this
indicated the time required for the incubation with the
chemicals. When a-tocopherol was
added to the growth medium at a physiological concentration of
50 µM, cell proliferation was inhibited by 40% in
72 h. A similar inhibitory effect of cell proliferation was
achieved when 500 µM SDH was used (39% inhibition in
72 h). From the doseresponse curves obtained it was
concluded that both duration of treatment and the concentration
of the chemicals are important parameters. The actual mechanism
of the inhibition of cell proliferation may be due to the
anti-oxidative potential of these chemicals as well as another
mechanism effecting signal transduction pathways.
Received 29 September 1998/19 November 1998; accepted 25
November 1998
Portland Press Ltd © 1999
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