Triptolide induces apoptosis of PMA-treated THP-1 cells through activation of caspases, inhibition of NF-κB and activation of MAPKs

Park,Seung-Won; Kim,Young  Il

doi:10.3892/ijo.2013.2033

Triptolide induces apoptosis of PMA-treated THP-1 cells through activation of caspases, inhibition of NF-κB and activation of MAPKs

Authors:
- Seung-Won Park
- Young Il Kim
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Affiliations: Department of Biotechnology, Catholic University of Daegu, Daegu 712-702, Republic of Korea, Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 130-872, Republic of Korea
Published online on: July 23, 2013 https://doi.org/10.3892/ijo.2013.2033
Pages: 1169-1175

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Abstract

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-κB (NF-κB) 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-κB 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-κB inhibition and the MAPK pathway.

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