TY - JOUR
T1 - 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
AU - Hsu, Ya Ling
AU - Kuo, Po Lin
AU - Tzeng, Tz Fei
AU - Sung, Shu Chiao
AU - Yen, Ming Hong
AU - Lin, Liang Tzung
AU - Lin, Chun Ching
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cell cycle
KW - Huang-lian-jie-du-tang
KW - Liver cancer
KW - Nuclear factor-kappa B (NF-κB)
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U2 - 10.1111/j.1440-1746.2008.05390.x
DO - 10.1111/j.1440-1746.2008.05390.x
M3 - Article
C2 - 18522681
AN - SCOPUS:47649092000
SN - 0815-9319
VL - 23
JO - Journal of Gastroenterology and Hepatology (Australia)
JF - Journal of Gastroenterology and Hepatology (Australia)
IS - 7 PT2
ER -