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

作者: Xiao-Hua Jiang , Benjamin Chun-Yu Wong , Marie Chia-Mi Lin , Geng-Hui Zhu , Hsiang-Fu Kung

DOI: 10.1038/SJ.ONC.1204981

关键词:

摘要: Triptolide, a major component in the extract of Chinese herbal plant Tripterygium wilfordii Hook f (TWHf), has potential anti-neoplastic effect. In present study we investigated therapeutic effects and mechanisms triptolide against human gastric cancer cells. Four cell lines with different p53 status, AGS MKN-45 (wild type p53); MKN-28 SGC-7901 (mutant p53) were observed as to growth inhibition induction apoptosis response treatment. We showed that inhibited growth, induced suppressed NK-kappaB AP-1 transactivation cells wild-type p53. Triptolide by stimulating expressions p53, p21(waf1/cip1), bax protein, increased activity caspases. addition, it caused cycle arrest G(0)/G(1) phase. To examine role these functions, suppression level antisense oligonucleotide abrogated triptolide-induced over-expression dominant negative abolished inhibitory effect on NF-kappaB activation. Furthermore, demonstrated had differential status. also whereas no significant growth-inhibition mutant Our data suggest exhibits anti-tumor anti-inflammatory inhibiting proliferation, inducing transcriptional activity. However, functional is required for proapoptotic, effects.

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