M. Hashimoto et al., RAPID FRAGMENTATION OF VIMENTIN IN HUMAN SKIN FIBROBLASTS EXPOSED TO TAMOXIFEN - A POSSIBLE INVOLVEMENT OF CASPASE-3, Biochemical and biophysical research communications, 247(2), 1998, pp. 401-406
Tamoxifen (TAM), an anti-estrogen compound, is widely used for chemoth
erapy of breast cancer, although the molecular mechanisms underlying T
AM cytotoxicity are obscure. Here, we show that TAM dramatically cause
d degradation of vimentin (VIM) in human skin fibroblasts, in a time a
nd dose dependent manner. Addition of caspase-3 inhibitor, Z-DEVD-FMK,
inhibited formation of some fragments of VIM, and caspase-3 was prote
olytically activated by TAM treatment. Expression of functional estrog
en receptors were negative in these cells, and neither transcription n
or protein synthesis was required for TAM-induced degradation of VIM.
Moreover, quinestrol, an ethinyl estradiol derivative, weakly degraded
VIM, whereas neither estradiols nor estriol had any effects. Taken to
gether, TAM may induce fragmentation of VIM associated with an activat
ion of caspase 3, which may be attributed to non-genomic actions of TA
M. (C) 1998 Academic Press.