Premium
Mono‐ubiquitination of annexin A1, acetylation of PML and apoptosis of MCF7 cells treated by HDAC inhibitors
Author(s) -
Hirata Aiko,
Senanayake Thulani H,
Woster Patrick M,
Hirata Fusao
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.834.5
Subject(s) - annexin , apoptosis , annexin a2 , acetylation , microbiology and biotechnology , cancer cell , chemistry , cancer research , annexin a5 , biology , cancer , biochemistry , genetics , gene
When MCF7 human breast adenocarcinoma cells were treated by HDAC inhibitors (HDACi), SAHA or THS79‐12, considerable portions of MCF7 cells became floated and underwent apoptosis. Annexin A1 in floated cells was mono‐ubiquitinated as determined by Western blots, suggesting that DNA was damaged. PML, a protein that plays an important role in DNA damage induced apoptosis was acetylated. Consequently, BclxL was induced, and caspase 3 was cleaved, demonstrating features of apoptosis. On the other hand, annexin A1 in attached cells was not ubiquitinated, and acetylation of PML did not occur. Cleavage of caspase 3 did not increase, showing no apoptotic changes. Annexin A1 was phosphorylated at tyrosine by EGF, and cell proliferation was reduced. MCF7 cells were morphologically differentiated. Contrary to the previously proposed hypothesis that induction of annexin A1 in cancer cells by HDACi causes apoptosis, our present observations suggest that two distinct responses to HDACi take place in attached and floating cells: in floating cells, deacetylation of PML is inhibited and oxidative stress is induced by HDACi, whereas in attached cells, annexin A1 induced by HDACi influences cell proliferation signaling by EGF. (Supported in parts by a grant from The Susan G. Komen Breast Cancer Foundation.)