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Relationship between lunasin's sequence and its inhibitory activity of histones H3 and H4 acetylation
Author(s) -
HernándezLedesma Blanca,
Hsieh ChiaChien,
de Lumen Ben O.
Publication year - 2011
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201000632
Subject(s) - acetylation , histone h4 , histone acetyltransferases , pcaf , bromodomain , histone , histone h3 , biology , biochemistry , histone acetyltransferase , p300 cbp transcription factors , lysine , creb binding protein , microbiology and biotechnology , creb , transcription factor , amino acid , gene
Scope: Dysfunction of histone acetyltransferases (HATs) or histone deacetylases (HDACs) involved in histones acetylation has been associated with cancer. Inhibitors of these enzymes are becoming potential targets for new therapies. Methods and Results: This study reports by Western‐Blot analysis, that peptide lunasin is mainly an in vitro inhibitor of histone H4 acetylation by P300/cAMP‐response element‐binding protein (CBP)‐associated factor (PCAF), with IC 50 values dependent on the lysine position sensitive to be acetylated (0.83 μM (H4‐Lys 8), 1.27 μM (H4‐Lys 12) and 0.40 μM (H4‐Lys 5, 8, 12, 16)). Lunasin is also capable of inhibiting H3 acetylation (IC50 of 5.91 μM (H3‐Lys 9) and 7.81 μM (H3‐Lys 9, 14)). Studies on structure‐activity relationship establish that lunasin's sequence are essential for inhibiting H4 acetylation whereas poly‐D sequence is the main active sequence responsible for H3 acetylation inhibition. Lunasin also inhibits H3 and H4 acetylation and cell proliferation (IC 50 of 181μM) in breast cancer MDA‐MB‐231 cells. Moreover, this peptide decreases expression of cyclins and cyclin dependent kinases‐4 and ‐6, implicated in cell cycle pathways. Conclusion: Results from this study demonstrates lunasin's role as modulator of histone acetylation and protein expression that might contribute on its chemopreventive properties against breast cancer.