there are various selective JAK inhibitors under development and investigation in phase 1 and 2 clinical trials. Modulating Bcl 2 family members, with the utilization of BH3 mimetics, including ABT 737, in combination with JAK2 inhibitors may be a promising c-Met inhibitor novel strategy for the treating MPD patients with mutant JAK2. Apoptosis and autophagy have been shown to be negatively controlled by prosurvival Bcl 2 proteins. We determined whether the anticancer agent celecoxib, alone or coupled with a little particle Bcl 2/Bcl xL villain, could produce autophagy in cancer of the colon cells. Moreover, we decided whether inhibition of autophagy could generate a cancerous colon cells into apoptosis. Celecoxib was demonstrated to induce apoptosis that was attenuated by ectopic Bcl 2 or Bax knockout. ABT Eumycetoma 737 synergistically superior celecoxib caused cytotoxicity that was primarily as a result of apoptosis as revealed by caspase cleavage and Annexin V labeling that was attenuated by a pan caspase inhibitor. Celecoxib triggered transformation of the autophagosome associated protein light chain 3 from a cytosolic to a membrane bound type, as shown by immunoblotting and a punctate uorescence structure of an ectopic GFP LC3 protein. Celecoxib induced conversion of LC3 was due to autophagy induction, as supported using the lysosome chemical, ba lomycin A1, which made an accumulation of LC3II. ABT 737 superior celecoxib induced LC3 transformation and p62/SQSTM1 destruction. Inhibition of autophagy was then analyzed in a e ort to drive cells in to apoptosis. 3 methyladenine blocked LC3 transformation, and 3 MA and wortmannin signi cantly increased apoptotic signaling in cells treated with celecoxib plus ABT 737. Furthermore, knockdown of Atg8/LC3B or Vps34 applying siRNA attenuated p62 degradation and increased apoptotic signaling, Vps34 siRNA potentiated annexin V, PI labeled cells caused by celecoxib ABT 737. To conclude, celecoxib induces apoptosis and autophagy Imatinib CGP-57148B that will equally be potentiated by ABT 737. Inhibition of autophagy was shown to enhance apoptosis, suggesting a novel therapeutic approach against cancer of the colon. Key words celecoxib, NSAID, ABT 737, Bcl 2, apoptosis, autophagy Introduction Colorectal cancer is the second major cause of cancer related death in the United States1 which underscores the requirement for effective techniques to treat and prevent this malignancy. Celecoxib is an NSAID and selective cyclooxygenase 2 inhibitor that can regress colon cancer xenografts and enhance the efficacy of chemotherapy and/or light treatment. Celecoxib may also regress/reduce the recurrence of pre-cancerous colon polyps in individuals, however, its protracted use was associated with cardiovascular toxicities. The antitumor effect of celecoxib is related to apoptosis induction, and this drug may engage the death receptor and the mitochondria mediated pathways.