Effects of St John's wort and hypericin on cytotoxicity of anticancer drugs.
St John's wort (SJW) is Hypericum perforatum L., Hypericaceae, a herbaceous perennial plant native to Europe and Asia, and its various preparations are widely used for the treatment of mild-to-moderately severe depressive disorders. With increasingly prevalent use, the interactions with SJW preparations with co-administered drugs have been reported, presumably via MDR1-mediated processes. In this paper, the effects of SJW extract on antiproliferative effects of anticancer drugs and the expression of MDR1 mRNA were examined using HeLa and its MDR1-overexpressing subline. The effects on MDR1-mediated transport were also evaluated using [(3)H]digoxin and LLC-GA5-COL150 cells, which were established by transfection of human MDR1 cDNA into porcine kidney epithelial LLC-PK(1) cells. The content of hypericin, a presumed active moiety within SJW extract, was determined by HPLC with a photo diode array to be 0.085 (w/w)%, and the effects of hypericin were also evaluated and compared with those of SJW extract. It was concluded that SJW extract reversed the cytotoxicity of paclitaxel and slightly of daunorubicin, down-regulated MDR1 mRNA, and inhibited MDR1-mediated transport, presumably due to other components than hypericin.
Wada
Atsushi
A
Department of Clinical Pharmacy, Kobe Pharmaceutical University, Japan.
Sakaeda
Toshiyuki
T
Takara
Kohji
K
Hirai
Midori
M
Kimura
Takashi
T
Ohmoto
Nobuko
N
Zhou
Jie
J
Nakamura
Tsutomu
T
Kobayashi
Hironao
H
Okamura
Noboru
N
Yagami
Tatsurou
T
Okumura
Katsuhiko
K