期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 43, 期 4, 页码 1169-1175出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2013.2033
关键词
apoptosis; caspase; nuclear factor-kappa B; mitogen-activated protein kinase; THP-1 cells; triptolide
类别
资金
- Bio-industry Technology DevelopmentProgram,Ministry for Food,Agriculture,Forestry and Fisheries, Republic of Korea [311059-4]
- Rural Development Administration, Republic of Korea [PJ008475022012]
- Rural Development Administration (RDA), Republic of Korea [PJ008475022012] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Triptolide is known to be involved in many cellular events, such as those related to immunosuppressive and antitumor activity. We investigated whether triptolide mediates these effects through multiple mechanisms, including activation of cell cycle arrest and caspase-dependent pathways, as well as by blocking nuclear factor-kappa B (NF-kappa B) activation and by potentiating the activities of the mitogen-activated protein kinase (MAPK) pathway, in phorbol myristate acetate (PMA)-differentiated THP-1 cells. Triptolide significantly inhibited cell proliferation in a dose- and time-dependent manner and it increased the apoptotic fraction in the cell cycle and the number of apoptotic THP-1 cells. Exposure of the cells to triptolide also increased caspase-3 activity in these cells. Furthermore, co-treatment of cells with triptolide and the pan-caspase inhibitor, Z-VAD-FMK, or the caspase-3 inhibitor, Z-DEVE-FMK, increased THP-1 cell growth. Triptolide treatment resulted in a significant decrease in mRNA expression levels in genes encoding Bcl-2, cyclin D1, p27 and survivin and an increase in those encoding Bax and p21 in THP-1 cells. Triptolide not only inhibited NF-kappa B activation, but also activated p38 MAPK and MEK/ERK phosphorylation. These results show that triptolide inhibits the growth of THP-1 cells by inducing apoptosis through caspase activation and the mechanism involves NF-kappa B inhibition and the MAPK pathway.
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