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Functional p53 is required for triptolide-induced apoptosis and AP-1 and nuclear factor-κB activation in gastric cancer cells

Oncogene volume 20, pages 8009–8018 (2001)Cite this article

Abstract

Triptolide, a major component in the extract of Chinese herbal plant Tripterygium wilfordii Hook f (TWHf), has potential anti-neoplastic effect. In the present study we investigated the potential therapeutic effects and mechanisms of triptolide against human gastric cancer cells. Four gastric cancer cell lines with different p53 status, AGS and MKN-45 (wild type p53); MKN-28 and SGC-7901 (mutant p53) were observed as to cell growth inhibition and induction of apoptosis in response to triptolide treatment. We showed that triptolide inhibited cell growth, induced apoptosis and suppressed NK-κB and AP-1 transactivation in AGS cells with wild-type p53. Triptolide induced apoptosis by stimulating the expressions of p53, p21waf1/cip1, bax protein, and increased the activity of caspases. In addition, it caused cell cycle arrest in the G0/G1 phase. To examine the role of p53 in these functions, we showed that suppression of p53 level with antisense oligonucleotide abrogated triptolide-induced apoptosis and over-expression of dominant negative p53 abolished the inhibitory effect on NF-κB activation. Furthermore, we demonstrated that triptolide had differential effects on gastric cancer cells with different p53 status. We showed that triptolide also inhibited cell growth and induced apoptosis in MKN-45 with wild-type p53, whereas it had no significant growth-inhibition and apoptosis induction effects on the MKN-28 and SGC-7901 cells with mutant p53. Our data suggest that triptolide exhibits anti-tumor and anti-inflammatory effects by inhibiting cell proliferation, inducing apoptosis and inhibiting NF-κB and AP-1 transcriptional activity. However, a functional p53 is required for these proapoptotic, anti-inflammatory and anti-tumor effects.

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Abbreviations

TWHf:

Tripterygium wilfordii Hook f

NF-κB:

nuclear factor-κB

AP-1:

Activator Protein-1

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Acknowledgements

This study is supported by Gastroenterological Research Fund, University of Hong Kong.

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Author notes

  1. Xiao-Hua Jiang and Benjamin Chun-Yu Wong: X-H Jiang and BC-Y Wong contributed equally to this work

Authors and Affiliations

  1. Department of Gastroenterology, Rui-jin Hospital, Shanghai, People's Republic of China

    Xiao-Hua Jiang & Shi-Hu Jiang

  2. Department of Medicine, University of Hong Kong, Hong Kong

    Xiao-Hua Jiang, Benjamin Chun-Yu Wong, Geng-Hui Zhu & Shiu-Kum Lam

  3. Institute of Molecular Biology, University of Hong Kong, Hong Kong

    Marie Chia-Mi Lin & Hsiang-Fu Kung

  4. Department of Chemistry, University of Hong Kong, Hong Kong

    Dan Yang

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  1. Xiao-Hua Jiang
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Correspondence to Benjamin Chun-Yu Wong.

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Jiang, XH., Wong, BY., Lin, MM. et al. Functional p53 is required for triptolide-induced apoptosis and AP-1 and nuclear factor-κB activation in gastric cancer cells. Oncogene 20, 8009–8018 (2001). https://doi.org/10.1038/sj.onc.1204981

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