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

Triptolide, a major component in the extract of Chinese herbal plant Tripte rygium wilfordii Hook f (TWHf), has potential anti-neoplastic effect. In th e present study we investigated the potential therapeutic effects and mecha nisms 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-kapp aB and AP-1 transactivation in AGS cells with wild-type p53. Triptolide ind uced apoptosis by stimulating the expressions of p53, p21(waf1/cip1), bax p rotein, 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 f unctions, we showed that suppression of p53 level with antisense oligonucle otide abrogated triptolide-induced apoptosis and over-expression of dominan t negative p53 abolished the inhibitory effect on NF-kappa dB activation. F urthermore, we demonstrated that triptolide had differential effects on gas tric 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 eff ects on the MKN-28 and SGC-7901 cells with mutant p53. Our data suggest tha t triptolide exhibits anti-tumor and anti-inflammatory effects by inhibitin g cell proliferation, inducing apoptosis and inhibiting NF-kappaB and AP-1 transcriptional activity. However, a functional p53 is required for these p roapoptotic, anti-inflammatory and anti-tumor effects.