Huang-lian-jie-du-tang, a traditional Chinese medicine prescription, induces cell-cycle arrest and apoptosis in human liver cancer cells in vitro and in vivo

Ya Ling Hsu, Po Lin Kuo, Tz Fei Tzeng, Shu Chiao Sung, Ming Hong Yen, Liang Tzung Lin, Chun Ching Lin

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42 Citations (Scopus)

Abstract

Background and Aim: Huang-lian-jie-du-tang (HLJDT; Japanese name, oren-gedoku-to) is a traditional Chinese medicine prescription known to possess anti-inflammatory activity. Our study reports here for the first time the anticancer effect of HLJDT in two human liver cancer cell lines, Hep G2 and PLC/PRF/5. Methods: Inhibition of cell proliferation by HLJDT was measured by sodium 3′-(1-(phenylamino-carbonyl)-3,4-tetrazolium)-bis(4-methoxy-6- nitro) benzene-sulfonic acid hydrate (XTT) assay. Clonogenic assay was used to elucidate the possible differences in long-term effects of HLJDT on human liver cancer cells. Cell cycle distribution was determined by flow cytometry. Apoptosis was detected using electrophoresis and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick endlabeling (TUNEL) assay. Protein expressions were determined by immunoblot assay. The activity of nuclear factor-kappa B (NF-κB) was determined by Trans-AM ELISA kit. In vivo tumor activity was assessed by xenograft study. Results: HLJDT significantly increased the expression of inactivated phospho-Cdc2 and phospho-Cdc25C, and decreased the levels of cyclin A, cyclin B1, Cdc2, and Cdc25C, thereby contributing to cell-cycle arrest. HLJDT increased the expression of Bax and Bak, but decreased the level of Bcl-2 and Bcl-XL, and subsequently triggered the mitochondrial apoptotic pathway. In addition, HLJDT also inhibited cell-survival signaling by enhancing the amount of IκBα in the cytoplasm, reducing the level and activity of NF-κB in the nucleus, and subsequently attenuating the expression of Bcl-XL in Hep G2 and PLC/PRF/5 cells. The inhibitory effect mediated by HLJDT on cell growth was also demonstrated in a nude mouse model, in which the liver cancer cells induced tumor xenograft shrank considerably following treatment with HLJDT. Conclusions: Taken together, these results suggest a potential anticancer effect of HLJDT against human liver cancer cells.

Original languageEnglish
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume23
Issue number7 PT2
DOIs
Publication statusPublished - 2008
Externally publishedYes

Keywords

  • Apoptosis
  • Cell cycle
  • Huang-lian-jie-du-tang
  • Liver cancer
  • Nuclear factor-kappa B (NF-κB)

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

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