Relationship between lunasin's sequence and its inhibitory activity of histones H3 and H4 acetylation

Blanca Hernández-Ledesma, Chia Chien Hsieh, Ben O. De Lumen

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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 IC50 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 (IC50 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.

Original languageEnglish
Pages (from-to)989-998
Number of pages10
JournalMolecular Nutrition and Food Research
Volume55
Issue number7
DOIs
Publication statusPublished - 2011 Jul 1

Keywords

  • Breast cancer cells
  • Cell proliferation
  • Histone acetylation
  • Lunasin
  • Protein biomarkers

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

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