it was consistent with our in vitro data showing that TW 37 is a powerful agent for the inhibition of cell development and induction of apoptosis, which can be mediated by inhibition HDAC inhibitors list of Bcl 2 family of proteins and its downstream genes, especially Notch 1 and NF jB. The Bcl 2 family of proteins plays essential roles in human cancers, including pancreatic cancer. The activation of Bcl 2 is shown to increase tumor growth, invasion, mobility, metastasis and tumor scattering, and inhibition of apoptosis. The overexpression of Bcl 2 family proteins in pancreatic cancer may also play significant roles in resistance to a wide spectrum of chemotherapeutic agents. For that reason, identification of a chemical targeting Bcl 2 family of proteins probably will give a therapeutic advantage for pancreatic cancer. Our laboratory and the others have extensively studied several small molecule inhibitors including gossypol, apogossypolone, together with TW 37 for their antitumor activity in several cancers. The current study reveals that TW 37 inhibits tumor growth and induces apoptosis of pancreatic cancer cells, which was partly mediated through inactivation of Notch 1 and NF nB signal Posttranslational modification pathways that are downstream of Bcl 2. . TW 37, a recently developed small molecule inhibitor of Bcl 2, is capable of antagonizing the event of pan Bcl 2 family and thus could have greater therapeutic potential as a totally new class of antitumor agent. We have unearthed that TW 37 inhibits the growth of a number of cancer cells, including pancreatic cancer cells. Here, we investigated the mechanism by which TW 37 elicits its biological effects on pancreatic cancer cells. In this research, we used two human pancreatic cancer cell lines, BxPC 3 and Colo 357. Both cell Foretinib price lines have high expression of Bcl 2, Bcl xL, and Mcl 1. . We found that TW 37 was capable of inducing substantial growth inhibition in both BxPC 3 and Co-lo 357 cells as detected by the clonogenic assay and the WST assay. More over, TW 37 also induced apoptotic cell death in both cell lines, suggesting that blocking Bcl 2 is sufficient to trigger apoptosis in pancreatic cancer cells overexpressing these compounds. To further elucidate the mechanism of action, we discovered whether cell cycle arrest was associated with the cell growth inhibition. Certainly, we found that TW 37 increased Figure 4. Effect of TW 37 on Notch 1 expression in human pancreatic cancer cells. A, the expression of Notch 1, its ligand Jagged 1, and its target gene Hes 1 was detected by Western blotting. T, the Co-lo 357 pancreatic cancer cells treated with 500 nmol/L TW 37 for 72 h were subjected to immunofluorescent staining using anti Notch 1 antibody and anti Jagged 1 antibody. C, the Notch 1 mRNAlevel was detected in Colo 357 mobile lines and 3 treated with TW 37 for 72 h as measured by real-time RT PCR. Cell growth was GSI significantly inhibited Colo 357 by D, top,. TW 37 plus GSI inhibited Colo 357 cell development to a better degree in contrast to TW 37.