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

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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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Document Type: Research Article

Affiliations: 1: Department of Biotechnology, Catholic University of Daegu, Daegu 712-702, Republic of Korea 2: Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 130-872, Republic of Korea

Publication date: January 1, 2013

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  • The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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