Pheophorbide a, an active component in Scutellaria barbata, reverses P-glycoprotein-mediated multidrug resistance on a human hepatoma cell line R-HepG2.
Scutellaria barbata, a Traditional Chinese Medicine native in southern China, has been widely used for treating liver diseases. In this study, the anti-proliferative effect of Pheophorbide a (Pa), an active component from S. barbata, was examined on a multi-drug resistant (MDR) human hepatoma cell line R-HepG2. Our study showed that Pa could significantly inhibit the growth of R-HepG2 cells with an IC50 value at 25.0 microM after 48 hours treatment. When compared with the parental HepG2 cells, Pa showed weak resistance to R-HepG2. Efflux of Pa out of R-HepG2 cells was not observed as its cellular uptake level showed no significant difference comparing with HepG2 cells. Interestingly, significant reduction of P-glycoprotein expression on Pa-treated R-HepG2 cells was found at both transcriptional and translational levels, leading to reduction of P-glycoprotein activity. In addition, mechanistic study elucidated that Pa induced cell cycle arrest at G2/M phase and inhibited the expressions of G2/M phase cell cycle regulatory proteins, cyclin-A1 and cdc2 in a dose-dependent manner.
Tang
Patrick Ming-Kuen
PM
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Chan
Judy Yuet-Wa
JY
Zhang
Dong-Mei
DM
Au
Shannon Wing-Ngor
SW
Fong
Wing-Ping
WP
Kong
Siu-Kai
SK
Tsui
Stephen Kwok-Wing
SK
Waye
Mary Mui-Yee
MM
Mak
Thomas Chung-Wai
TC
Fung
Kwok-Pui
KP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D031363:Scutellaria / Q000737:chemistry*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002734:Chlorophyll; C032623:pheophorbide a