A novel HDAC inhibitor, Scriptaid, has been found to have robust activity and lower toxicity compared to trichostatin A (TSA). Although Scriptaid induced activation of both p38MAPK and JNK, it was the inhibition of JNK that attenuated Scriptaid-induced apoptosis significantly. Scriptaid also increased the expression of (i) p21 and p27 involved in cell-cycle regulation and (ii) γH2AX associated with DNA damage response in a JNK-dependent manner.