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Abstract Title:

Reversal of P-glycoprotein-mediated multidrug resistance in human hepatoma cells by hedyotiscone A, a compound isolated from Hedyotis corymbosa.

Abstract Source:

Xenobiotica. 2012 Feb 21. Epub 2012 Feb 21. PMID: 22352391

Abstract Author(s):

Grace Gar-Lee Yue, Julia Kin-Ming Lee, Ling Cheng, Ben Chung-Lap Chan, Lei Jiang, Kwok-Pui Fung, Ping-Chung Leung, Clara Bik-San Lau

Article Affiliation:

Institute of Chinese Medicine , Shatin, New Territories, Hong Kong , China.

Abstract:

Multidrug resistance is a major problem in hepatocellular carcinoma. Hedyotiscone A, a compound isolated from Chinese herbal medicine Hedyotis corymbosa (HC, family Rubiaceae), was used as the chemical marker to distinguish between HC and an anticancer herb Hedyotis diffusa (HD) in our previous study. The present study aimed to investigate whether HA exhibited antiproliferative activities in multidrug-resistant hepatocellular carcinoma cells R-HepG2 and the parental cells HepG2 using MTT assay and [(3)H]-thymidine incorporation assay. Our results showed that HA could significantly inhibit cell proliferation in R-HepG2 and HepG2 (IC(50) = 43.7 and 56.3 µg/mL, respectively), but not in normal human liver cells WRL-68 (IC(50)>100µg/mL) cells, suggesting its selective cytotoxic effects. Besides, HA induced apoptosis in R-HepG2 cells, as confirmed by annexin-V&propidium iodide staining, and DNA fragmentation assay. The caspase cascade was activated as shown by a significant increase of cleaved caspases-3, -7 and -9 in HA-treated R-HepG2 cells. The activities and protein expression of P-glycoprotein as well as mRNA expression of MDR1 were also decreased in HA-treated R-HepG2 cells. Our study demonstrated for the first time the antiproliferative activities of hedyotiscone A in multidrug-resistant R-HepG2 cells. The findings revealed the potential of this compound in treating multidrug-resistant tumor.

Study Type : In Vitro Study

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Sayer Ji
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