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Inhibition of polyisoprenylated protein metabolism may explain the apoptotic properties of farnesol and related flavors
Author(s) -
AyukTakem Lambert Tiku,
Amissah Felix,
Lamango Nazarius S
Publication year - 2010
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/fasebj.24.1_supplement.565.7
Subject(s) - farnesol , chemistry , geraniol , terpene , stereochemistry , biochemistry , chromatography , essential oil
Polyisoprenylation is the modification of about 2% of eukaryotic proteins involving the reaction of trans, trans ‐farnesyl or all trans ‐geranylgeranyl groups to a C‐terminal cysteine. The –COOH of the cysteine is methylated by polyisoprenylated protein methyl transferase (PPMTase) into esters which are then hydrolyzed by polyisoprenylated methylated protein methyl esterase (PMPMEase). Because aberrant polyisoprenylated protein activity is associated with ~30% of cancers, compounds that modulate their metabolism may be useful as anticancer agents. Farnesol and related compounds are natural food components or flavors that are derived from citrus, ginger, teas and chamomile. They are structurally related to the polyisoprenyl moieties of polyisoprenylated proteins and may thus inhibit PMPMEase. When PMPMEase was incubated with the PMPMEase substrate, RD‐PNB, farnesol, trans, trans ‐farnesol, citronellal, α‐Ionone, eugenol and geraniol inhibited the enzyme activity with Ki values of 1.9, 5.5, 6.6, 3, 15 and 45 μM, respectively. Farnesol and trans, trans ‐farnesol induced the degeneration of human lung A549, colorectal Caco‐2 and neuroblastoma SH‐SY5Y cancer cells with EC 50 values of 18 and 19, 14 and 19 and 265 and 465 μM, respectively. These suggest that the apoptotic effects of these compounds may be associated with PMPMEase inhibition, suggesting the latter may be a viable anticancer target.