Dracorhodin perchlorate has been recently shown to induce apoptotic cell death 
in cancer cells. However, the molecular mechanisms underlying these effects are 
unknown in human gastric tumor cells. In this study, effects of Dracorhodin 
perchlorate on cell viability, cell cycle, and apoptosis were investigated in 
SGC-7901 cells. The results showed that Dracorhodin perchlorate induced cellular 
and DNA morphological changes and decreased the viability of SGC-7901 cells. 
Dracorhodin perchlorate-mediated cell cycle arrest was associated with a marked 
decrease in protein levels of phosphorylated retinoblastoma and E2F1. 
Dracorhodin perchlorate-induced apoptosis is mediated via upregulation of p53, 
inhibiting the activation of PI3K/Akt, and NF-κB, thereby decreasing the 
expression of the anti-apoptotic proteins, Bcl-2 and Bcl-XL. Interestingly, we 
also found that Dracorhodin perchlorate significantly suppressed the 
IGF-1-induced phosphorylation of Akt in the stably expressing EGFP-Akt 
recombinant CHO-hIR cells and inhibited TNF-induced NF-κB transcriptional 
activity in the NF-κBp65-EGFP recombinant U2OS cells, indicating that inhibition 
of PI3K/Akt and NF-κB may provide a molecular basis for the ability of 
Dracorhodin perchlorate to induce apoptosis. Dracorhodin perchlorate induced 
up-regulation of p53, thereby resulting in the activation of its downstream 
targets p21 and Bax following the dissipation of mitochondrial membrane 
potential and activation of caspase-3 and its substrate, PARP. Moreover, 
Dracorhodin perchlorate dramatically enhanced the wortmannin- and TNF-induced 
apoptosis in SGC-7901 cells. These results reveal functional interplay among the 
PI3K/Akt, p53 and NF-κB pathways that are frequently deregulated in cancer and 
suggest that their simultaneous targeting by Dracorhodin perchlorate could 
result in efficacious and selective killing of cancer cells.