TDP1 and hepatocellular carcinoma: Reports have shown that the treatment by Saffron bio-active compounds, especially Safranal, increases TOP1, phosphorylates histone H2AX, decreases HDAC1 expression, and phosphorylates histone H3, and TDP1 in a time-dependent manner resulting in enhanced DNA damage in HCC cell lines (HepG2) [93].