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Ferrocene‐induced lymphocyte activation and antitumor activity is mediated by redox‐sensitive signaling
Author(s) -
Kovjazin Riva,
Eldar Tova,
Patya Miriam,
Vanichkin Alexey,
Lander Harry M.,
Novogrodsky Abraham
Publication year - 2003
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/fj.02-0558fje
Subject(s) - ferrocene , jurkat cells , chemistry , microbiology and biotechnology , immune system , signal transduction , biochemistry , biology , t cell , immunology , electrode , electrochemistry
Ferrocene, a stable, synthetic, iron‐containing compound induces in vitro and in vivo activation of mouse lymphocytes and macrophages. Ferrocene also has a marked antitumor effect in mice, upon its administration intraperitoneally and in drinking water. Ferrocene's antitumor activity is attributed to its immune‐stimulatory property. This conclusion is supported by adoptive transfer experiments demonstrating that immune cells from ferrocene‐treated tumor‐bearing mice elicit an antitumor effect in mice not treated with ferrocene. We postulate that the immune stimulatory effect of ferrocene is mediated by redox‐sensitive signaling such as activation of p21 ras . This postulation is supported by the following findings: Ferrocene generates H 2 O 2 by autooxidation; N ‐acetylcysteine, a free‐radical scavenger, reduces its antitumor effect; and it stimulates GTPase activity catalyzed by pure recombinant p21 ras and activates ERK 1/2 in wild Jurkat T cells but fails to do so in the Jurkat T cells expressing p21 ras in which cysteine 118 was replaced by serine. Lastly, ferrocene activates and translocates NF‐kB in human PBM, a pathway which is mediated by ras. It is most plausible that additional redox‐sensitive signaling proteins mediate the biological effects of ferrocene.