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 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.
Hashimoto
M
M
School of Medicine, University of California, San Diego, La Jolla, California, 92093-0624, USA. mhashimoto@ucsd.edu
Inoue
S
S
Ogawa
S
S
Conrad
C
C
Muramatsu
M
M
Shackelford
D
D
Masliah
E
E
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D014746:Vimentin / Q000378:metabolism*
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D010446:Peptide Fragments; D014746:Vimentin; D013629:Tamoxifen; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases