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Rubber plant (Hevea brasiliensis) extract inhibits polyisoprenylated methylated protein methyl esterase and cancer cell viability
Author(s) -
Hester Ulyssa N,
Amissah Felix,
Aguilar Byron,
Duverna Randolph,
Lamango Nazarius
Publication year - 2012
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.26.1_supplement.612.6
Subject(s) - lncap , hevea brasiliensis , chemistry , viability assay , ethidium bromide , enzyme , biochemistry , acridine orange , cancer cell , esterase , apoptosis , cancer , biology , natural rubber , organic chemistry , dna , genetics
The polyisoprenylation pathway enzymes have been targeted for anticancer studies because aberrant polyisoprenylated protein activity is associated with ~30% of cancers. Polyisoprenylated methylated protein methyl esterase (PMPMEase) is a pivotal enzyme involved in the only reversible and possibly regulatory terminal reaction of the pathway. Inhibitors of PMPMEase have been shown to cause cell degeneration and so may be useful as anticancer agents. Hevea brasiliensis is a popular tropical commercial plant and a rich source of rubber, a polyterpene. We therefore propose that it may contain natural polyisoprenyl moieties which may inhibit PMPMEase. Enzyme assays revealed that methanolic extract of H. brasiliensis significantly inhibits PMPMEase activity. The most inhibitory fraction of extract also inhibited the viability of human breast cancer MDA‐MB‐231 and prostate cancer Lncap cells after 72 h exposure with EC50 values of 13 and 15 ìg/mL, respectively. Analysis with ethidium bromide/acridine orange suggests apoptosis as the mode of cell death. PMPMEase assays in MDA‐MB‐231 and Lncap cells also showed decreased enzyme activity after 24 h exposure. Consistent with previous studies using PMPMEase inhibitors, the apoptotic effects of the H. brasiliensis extract are most likely due to PMPMEase inhibition. Thus some of the isoprene compounds in the plant may be useful in anti‐cancer therapy.