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Genistein down‐regulates the constitutive activation of nuclear factor‐ κ B in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis
Author(s) -
He Hui,
Chen Laurie,
Zhai Ming,
Chen John Z. S.
Publication year - 2009
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.2715
Subject(s) - genistein , protein kinase b , apoptosis , cyclin d1 , cancer research , cell growth , cell culture , biology , transcription factor , pi3k/akt/mtor pathway , cell cycle , microbiology and biotechnology , chemistry , endocrinology , biochemistry , gene , genetics
Because of the central role of transcription factor nuclear factor‐ κ B (NF‐ κ B) in cell survival and proliferation in human multiple myeloma, the possibility of using it as a target for myeloma treatment was explored using genistein, an agent known to have very little or no toxicity in humans. It was found that NF‐ κ B was constitutively active in two human myeloma cell lines examined and that genistein, a chemopreventive agent, down‐regulated NF‐ κ B in two cell lines as indicated by the electrophoretic mobility gel shift assay and prevented the nuclear retention of p65 as shown by immunocytochemistry. Two myeloma cell lines showed constitutively active Akt phosphorylation. Genistein suppressed the constitutive Akt phosphorylation. Genistein also down‐regulated the expression of NF‐ κ B‐regulated gene products, including bcl‐2, bcl‐xl, cyclin D1 and ICAM‐1. This led to the suppression of proliferation and induction of apoptosis. Overall, the results indicate that genistein down‐regulates NF‐ κ B and phospho‐Akt in human myeloma cells, leading to the suppression of proliferation and induction of apoptosis, thus providing the molecular basis for the treatment of myeloma patients with this pharmacologically safe agent. Copyright © 2008 John Wiley & Sons, Ltd.