title: Pheophorbide a, an active component in Scutellaria barbata, reverses P-glycoprotein-mediated multidrug resistance on a human hepatoma cell line R-HepG2.
abstract: 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.
authors: Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors: Patrick Ming-Kuen
authors: PM
authors: Tang
authors: Judy Yuet-Wa
authors: JY
authors: Chan
authors: Dong-Mei
authors: DM
authors: Zhang
authors: Shannon Wing-Ngor
authors: SW
authors: Au
authors: Wing-Ping
authors: WP
authors: Fong
authors: Siu-Kai
authors: SK
authors: Kong
authors: Stephen Kwok-Wing
authors: SK
authors: Tsui
authors: Mary Mui-Yee
authors: MM
authors: Waye
authors: Thomas Chung-Wai
authors: TC
authors: Mak
authors: Kwok-Pui
authors: KP
authors: Fung
mesh_terms: 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*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002734:Chlorophyll; C032623:pheophorbide a