Perillyl alcohol inhibits human breast cancer cell growth in vitro and in vivo.
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.
Yuri
Takashi
T
Department of Pathology II, Kansai Medical University, Moriguchi, Osaka, Japan.
Danbara
Naoyuki
N
Tsujita-Kyutoku
Miki
M
Kiyozuka
Yasuhiko
Y
Senzaki
Hideto
H
Shikata
Nobuaki
N
Kanzaki
Hideharu
H
Tsubura
Airo
A
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
D000970:Antineoplastic Agents; D016213:Cyclins; D039821:Monoterpenes; D018809:Proliferating Cell Nuclear Antigen; D011960:Receptors, Estrogen; C032208:perillyl alcohol