RRC ID 61661
Author Jiang XH, Wong BC, Lin MC, Zhu GH, Kung HF, Jiang SH, Yang D, Lam SK.
Title Functional p53 is required for triptolide-induced apoptosis and AP-1 and nuclear factor-kappaB activation in gastric cancer cells.
Journal Oncogene
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-kappaB and AP-1 transactivation in AGS cells with wild-type p53. Triptolide induced apoptosis by stimulating the expressions of p53, p21(waf1/cip1), bax protein, and increased the activity of caspases. In addition, it caused cell cycle arrest in the G(0)/G(1) 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-kappaB 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-kappaB and AP-1 transcriptional activity. However, a functional p53 is required for these proapoptotic, anti-inflammatory and anti-tumor effects.
Volume 20(55)
Pages 8009-18
Published 2001-11-29
DOI 10.1038/sj.onc.1204981
PMID 11753684
MeSH Apoptosis / drug effects* Blotting, Western Caspase 3 Caspases / metabolism Cell Cycle / drug effects Cell Division / drug effects Cyclin-Dependent Kinase Inhibitor p21 Cyclins / metabolism DNA / genetics DNA / metabolism Diterpenes / pharmacology* Dose-Response Relationship, Drug Electrophoretic Mobility Shift Assay Epoxy Compounds Flow Cytometry Gene Expression Regulation, Neoplastic / drug effects Humans NF-kappa B / metabolism* Oligonucleotides, Antisense / genetics Phenanthrenes* Poly(ADP-ribose) Polymerases / metabolism Protein Binding / drug effects Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-bcl-2* Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology* Transcription Factor AP-1 / metabolism* Transcriptional Activation / drug effects Tumor Cells, Cultured Tumor Suppressor Protein p53 / biosynthesis Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism* bcl-2-Associated X Protein
IF 7.971
Human and Animal Cells MKN45(RCB1001)