NF-kappab facilitates oridonin-induced apoptosis and autophagy in HT1080 cells through a p53-mediated pathway.
In this study, we investigated the molecular mechanisms involving in oridonin-induced apoptosis and autophagy. We found that apoptosis and autophagy were simultaneously induced by oridonin time-dependently in HT1080 cells, and inhibition of autophagy by 3MA decreased oridonin-induced apoptosis, indicating that they act in synergy to mediate cell death. In addition, treatment with oridonin caused an increase in NF-kappaB and p53 activities in a time-dependent manner. Inhibition of NF-kappaB or p53 activation by its specific inhibitor PDTC or pifithrin-alpha respectively, significantly reduced both oridonin-induced apoptosis and autophagy accompanied by the decrease in Beclin 1 and LC3 levels. Further experiments confirmed that oridonin-induced p53 activation was reduced by the NF-kappaB inhibitor whereas the activation of NF-kappaB was not affected by p53 inhibition. Taken together, these results demonstrate that NF-kappaB promotes oridonin-induced apoptotic and autophagic cell death through regulating p53 activation in HT1080 cells.
Zhang
Yahong
Y
China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
Wu
Yingliang
Y
Wu
Di
D
Tashiro
Shin-ichi
S
Onodera
Satoshi
S
Ikejima
Takashi
T
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D052160:Benzothiazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D052160:Benzothiazoles; D045786:Diterpenes, Kaurane; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; C495901:TP53 protein, human; D013859:Thiocarbamates; D016159:Tumor Suppressor Protein p53; C011959:oridonin; C066229:prolinedithiocarbamate; D014050:Toluene; D011392:Proline; C121565:pifithrin