Panobinostat and sodium butyrate can inhibit cancer cell growth in vitro and in vivo as a result of selective induction of endogenous genes that play significant roles in G1-S progression. The histone variant H2A.Z has been shown to bind to the promoter of p21 at the p53 binding sites in p53+/+ cells. In response to stress, H2A.Z is evicted to allow p53 to bind which leads to p21 expression. The p400 complex takes part in this pathway and was proposed to be responsible for H2A.Z deposition into the p21 promoter. Depleting p400 by siRNA increases p21 expression in a p53 dependent manner and induces premature senescence. The mechanism of this activation is unclear. In the ERa-negative breast cancer cell line MDA-MB231 p53 is mutated and non-functional. Here we show that activation of p21 in response to HDACi treatment of these ERa-negative cells requires H2A.Z acetylation and exchange at its transcription start site. Cancer is a multi-step process resulting from acquired genetic and epigenetic alterations that abrogate normal control of cellular functions and eventually lead to uncontrollable cell growth and proliferation. In SJN 2511 recent years, the advances in understanding the molecular basis of cancer have led to a significant improvement of diagnostics and therapeutics for a better management of diseases. However, a number of chemotherapeutic agents that exert chemotherapeutic action through their ability to inhibit nuclear DNA topoisomerases have been the mainstay of cancer treatment for many decades. Tops are evolutionally conserved nuclear enzymes, which are essential for DNA metabolism where they are involved in generating the necessary topological state of DNA during replication, transcription, recombination, and chromatin remodeling. Tops act by introducing a sequential breakage and rejoining of one DNA strand or both DNA strands allowing DNA to be transformed between topological isoforms. Therefore, these enzymes have been identified as important targets for cytotoxic drugs and their inhibitors are widely used for decades in cancer chemotherapy. The Top inhibitors can be classified into two classes according to their mechanism of action: Top poisons and RAD001 159351-69-6 catalytic inhibitors. Top poisons, such as camptothecin and etoposide are able to stabilize the covalent complexes between the enzyme and DNA, termed cleavable complex, and prevent the rejoining step of the reaction thereby resulting in accumulation of DNA strand break. Consequently, tumor cell death is triggered by the substantial DNA damage evoked by Top poisons. On the other hand, the catalytic inhibitors act on any of the other steps in the catalytic cycle by preventing the binding between Top and DNA or interfering with the binding or release of ATP, resulting in activating the decatenation checkpoint. We report here a symmetric bibenzimidazole derivative, STK295900, as a Top catalytic inhibitor. STK295900 efficiently inhibited the growth of various cancer cell lines such as HeLa, MCF7, HepG2, and HL-60. In addition, cells treated with STK295900 were arrested in G2 phase without activation of DNA damage checkpoint. These findings may therefore suggest a potential development of symmetric bibenzimidazole as a chemotherapeutic agent. In the search for new chemotherapeutic agents from the small molecule library.