Advances in Traditional Medicine

Kyung Hee Oriental Medicine Research Center (경희대학교 융합한의과학연구소)
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Artemisia capillaris Thunb. inhibits cell growth and induces apoptosis in human hepatic stellate cell line LX2

  • Kim, Young-Il (Medical Science Research Institute, Kyung Hee University Medical Center) ;
  • Lee, Jang-Hoon (Department of Internal Medicine, College of Oriental Medicine, Kyung Hee University) ;
  • Park, Seung-Won (Department of Agricultural Biology, National Academy of Agricultural Science) ;
  • Choi, In-Hwa (Department of Oriental Ophthalmology, Otorhinolaryngology and Dermatology, East-West Neo Medical Center, Kyung Hee University) ;
  • Friedman, Scott L. (Division of Liver Diseases, Mount Sinai School of Medicine) ;
  • Woo, Hong-Jung (Department of Internal Medicine, College of Oriental Medicine, Kyung Hee University) ;
  • Kim, Young-Chul (Department of Internal Medicine, College of Oriental Medicine, Kyung Hee University)
  • Received : 2010.09.15
  • Accepted : 2010.12.01
  • Published : 2010.12.31
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Abstract

Artemisia capillaris (A. capillaries) is known to play roles in many cellular events, such as cell proliferation, differentiation, and apoptosis. We investigated the antifibrogenic efficacy of A. capillaris in the immortalized human hepatic stellate cell line LX2. Cell proliferation was determined by the MTT assay. Cell cycle was analyzed by the flow cytometry. Apoptotic cells were measured using a cell death detection ELISA. Caspase activity was detected by a colorimetric assay. The mRNA level of Bcl-2 and Bax mRNA were measured by real-time PCR. MEK and ERK protein were detected by Western blot analysis. We provide evidence that A. capillaris induces cell cycle arrest, apoptosis, and potently inhibits the mitogen-activated protein kinase pathway. A. capillaris inhibited cell proliferation of LX2 cells in a dose- and time-dependent manner, increased the apoptosis fraction at cell cycle analysis with an accompanying DNA fragmentation, and resulted in a significant decrease in Bcl-2 mRNA levels and an increase in Bax expression. Exposure of LX2 cells to A. capillaris induced caspase-3 activation, but co-treatment of A. capillaris with the pan-caspase inhibitor Z-VAD-FMK, and the caspase-3 inhibitor Z-DEVE-FMK, blocked apoptosis. A. capillaris down-regulated Mcl-1 protein levels and inhibited phosphorylation of MEK/ERK, suggesting that it mediates cell death in LX2 cells through the down-regulation of Mcl-1 protein via a MEK/ERK-independent pathway.

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References

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