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Rapid fragmentation of vimentin in human skin fibroblasts exposed to tamoxifen: a possible involvement of caspase-3.

Abstract：

:Tamoxifen (TAM), an anti-estrogen compound, is widely used for chemotherapy of breast cancer, although the molecular mechanisms underlying TAM cytotoxicity are obscure. Here, we show that TAM dramatically caused degradation of vimentin (VIM) in human skin fibroblasts, in a time and dose dependent manner. Addition of caspase-3 inhibitor, Z-DEVD-FMK, inhibited formation of some fragments of VIM, and caspase-3 was proteolytically activated by TAM treatment. Expression of functional estrogen receptors were negative in these cells, and neither transcription nor 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 together, TAM may induce fragmentation of VIM associated with an activation of caspase-3, which may be attributed to non-genomic actions of TAM.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Hashimoto M,Inoue S,Ogawa S,Conrad C,Muramatsu M,Shackelford D,Masliah E

doi

10.1006/bbrc.1998.8799

subject

Has Abstract

pub_date

1998-06-18 00:00:00

pages

401-6

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(98)98799-X

journal_volume

247

pub_type

杂志文章

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