Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The monoterpene d-limonene inhibits the post-translational isoprenylation of p21ras and other small G proteins, a mechanism that may contribute to its efficacy in the chemoprevention and therapy of chemically induced rodent cancers. In the present study, the relative abilities of 26 limonene-like monoterpenes to inhibit protein isoprenylation and cell proliferation were determined. Many monoterpenes were found to be more potent than limonene as inhibitors of small G protein isoprenylation and cell proliferation. The relative potency of limonene-derived monoterpenes was found to be: monohydroxyl = ester = aldehyde > thiol > acid = diol = epoxide > triol = unsubstituted. All monoterpenes that inhibited protein isoprenylation did so in a selective manner, such that 21-26 kDa proteins were preferentially affected. Perillyl alcohol, one of the most potent terpenes, reduced 21-26 kDa protein isoprenylation to 50% of the control level at a concentration of 1 mM, but had no effect on the isoprenylation of 67, 47 or 17 kDa proteins. In particular, p21ras farnesylation was inhibited 40% by 1 mM perillyl alcohol. At the same concentration, perillyl alcohol completely inhibited the proliferation of human HT-29 colon carcinoma cells. The structure-activity relationships observed among the monoterpene isoprenylation inhibitors support a role for small G proteins in cell proliferation, and suggest that many limonene-derived monoterpenes warrant further investigation as antitumor agents.
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PMID:Structure-activity relationships among monoterpene inhibitors of protein isoprenylation and cell proliferation. 818 48