toxicity (Figure 6A). This finding supports the contention that aciculatin does exhibit anti-tumor activity in living organisms. Immunohistochemical (IHC) staining showed that the p53 protein was upregulated in aciculatin-treated tumor tissues. This proved the importance of p53 in vivo (Figure 6B). In conclusion, these results show that aciculatin is a potent p53 inducer and potent anti-tumor flavonoid with low genotoxicity. This study also provides insights into the relationship between MDM2 depletion and p53 accumulation. An interesting question that remains to be answered is whether there is any correlation between these promising effects and DNA-binding activity. If so, the integrity of the aciculatin structure becomes important, and the uncommon tight C-glycoside linkage could conserve the compound, rendering it indestructible in the cellular environment. 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