title: Perillyl alcohol inhibits human breast cancer cell growth in vitro and in vivo.
abstract: The effect of monoterpene perillyl alcohol (POH) on cell growth, cell cycle progression, and expression of cell cycle-regulatory proteins in estrogen receptor (ER)-positive (KPL-1 and MCF-7) and ER-negative (MKL-F and MDA-MB-231) human breast cancer cell lines was examined. POH inhibited cell proliferation in a dose-dependent manner in all cell lines tested. POH at a dose of 500 micro M had a cytostatic effect, in which growth inhibition was due to accumulation of cells in G1-phase. Cell cycle progression was preceded by a decrease in G1 cyclins (cyclin D1 and E), followed by an increase in p21(Cip1/Waf1) and a decrease in proliferating cell nuclear antigen level. Levels of p53 and cyclin A were unchanged. POH at a dose of 75 mg/kg administered intraperitoneally three times a week throughout the entire 6-week experimental period suppressed orthotopically transplanted KPL-1 tumor cell growth and regional lymph node metastasis in a nude mouse system. POH inhibited both ER-positive and -negative human breast cancer cell growth in vitro, and suppressed growth and metastasis in vivo.
authors.affiliation: Department of Pathology II, Kansai Medical University, Moriguchi, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yuri
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Danbara
authors.forename: Miki
authors.initials: M
authors.lastname: Tsujita-Kyutoku
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kiyozuka
authors.forename: Hideto
authors.initials: H
authors.lastname: Senzaki
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shikata
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kanzaki
authors.forename: Airo
authors.initials: A
authors.lastname: Tsubura
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D016213:Cyclins / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007263:Infusions, Parenteral; D051379:Mice; D008819:Mice, Nude; D039821:Monoterpenes / Q000494:pharmacology*; D009362:Neoplasm Metastasis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011960:Receptors, Estrogen; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016213:Cyclins; D039821:Monoterpenes; D018809:Proliferating Cell Nuclear Antigen; D011960:Receptors, Estrogen; C032208:perillyl alcohol