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- Title
Ferrocene‐induced lymphocyte activation and antitumor activity is mediated by redox‐sensitive signaling.
- Authors
Kovjazin, Riva; Eldar, Tova; Patya, Miriam; Vanichkin, Alexey; Lander, Harry M.; Novogrodsky, Abraham
- Abstract
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 p21ras. This postulation is supported by the following findings: Ferrocene generates H2O2 by autooxidation; N‐acetylcysteine, a free‐radical scavenger, reduces its antitumor effect; and it stimulates GTPase activity catalyzed by pure recombinant p21ras and activates ERK 1/2 in wild Jurkat T cells but fails to do so in the Jurkat T cells expressing p21ras 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.
- Publication
FASEB Journal, 2003, Vol 17, Issue 3, p1
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.02-0558fje