Farnesyl-O-acetylhydroquinone and geranyl-O-acetylhydroquinone suppress the proliferation of murine B16 melanoma cells, human prostate and colon adenocarcinoma cells, human lung carcinoma cells, and human leukemia cells.
Farnesyl-O-acetylhydroquinone (IC(50)=2.5 microM/l) suppressed the proliferation of murine B16F10 melanoma cells with a potency much greater than those of farnesol (IC(50)=45 microM/l) and farnesyl anthranilate (IC(50)=46 microM/l), its alcohol, and ester counterparts with proven anti-tumor activities in vivo. Geranyl-O-acetylhydroquinone (IC(50)=5.1 microM/l) also had a much-improved activity compared to geraniol (IC(50)=160 microM/l) and geranyl anthranilate (IC(50)=30 microM/l). The suppression by farnesyl-O-acetylhydroquinone was concentration- and time-dependent and was accompanied by arrest of cell cycle at G1 and G2/M phases as shown by flow cytometry. Farnesyl-O-acetylhydroquinone and lovastatin had additive impact on B16 cell proliferation. Farnesyl-O-acetylhydroquinone also suppressed the proliferations of human cancer cells HL-60, DU145, PC-3, LNCaP, Caco-2, and A549. Our results suggested that farnesyl derivatives, suppressors of tumor 3-hydroxy-3-methylglutaryl coenzyme A reductase activities, have potential as chemopreventive or chemotherapeutic agents.
McAnally
Jennifer A
JA
Department of Biology, Texas Woman's University, Denton, TX 76204, USA.
Jung
Manfred
M
Mo
Huanbiao
H
D000818:Animals; D000970:Antineoplastic Agents; D000971:Antineoplastic Combined Chemotherapy Protocols; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005204:Farnesol / Q000031:analogs & derivatives / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology*; D066298:In Vitro Techniques; D008148:Lovastatin / Q000494:pharmacology; D051379:Mice; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
D000970:Antineoplastic Agents; D006873:Hydroquinones; D013729:Terpenes; C481440:farnesyl-O-acetylhydroquinone; C481439:geranyl-O-acetylhydroquinone; D005204:Farnesol; D008148:Lovastatin