Ferrocene-induced lymphocyte activation and anti-tumor activity is mediated by redox-sensitive signaling.

Riva Kovjazin, Tova Eldar, Miriam Patya, Alexey Vanichkin, Harry M. Lander, Abraham Novogrodsky

Research output: Contribution to journalArticlepeer-review

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-kappaB 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.

Original languageEnglish
Pages (from-to)467-469
Number of pages3
JournalFASEB Journal
Volume17
Issue number3
DOIs
StatePublished - Mar 2003
Externally publishedYes

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