RAPID FRAGMENTATION OF VIMENTIN IN HUMAN SKIN FIBROBLASTS EXPOSED TO TAMOXIFEN - A POSSIBLE INVOLVEMENT OF CASPASE-3

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.