Effects of reactive oxygen species on cell proliferation and death in HeLa cells and its MDR1-overexpressing derivative cell line.
In this paper, the effects of H2O2, a typical reactive oxygen species (ROS), on cell proliferation or death were examined using the human cervical carcinoma cell line HeLa and its MDR1-overexpressing subline, Hvr100-6, which was established by stepwise exposure to vinblastine. It was confirmed that the growth of HeLa cells was enhanced by H2O2 at relatively low concentrations in a concentration-dependent manner, and the growth enhancement was suppressed by antioxidants. Doxorubicin and daunorubicin also enhanced the growth of HeLa cells at concentrations lower than IC50 values, and the antioxidants suppressed this effect, being consistent with the fact that both anticancer drugs generate ROS. The growth enhancement by H2O2 or doxorubicin and daunorubicin was not observed in Hvr100-6 cells. In addition, it was suggested that antioxidants had no effect on MDR1 mRNA expression in HeLa and Hvr100-6 cells, and thereby hardly reverse multidrug resistance in tumor cells.
Liu
Yu-Wen
YW
Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan.
Sakaeda
Toshiyuki
T
Takara
Kohji
K
Nakamura
Tsutomu
T
Ohmoto
Nobuko
N
Komoto
Chiho
C
Kobayashi
Hironao
H
Yagami
Tatsurou
T
Okamura
Noboru
N
Okumura
Katsuhiko
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006131:Growth Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D017382:Reactive Oxygen Species / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006131:Growth Inhibitors; D017382:Reactive Oxygen Species