It has been shown that metformin could selectively target cancer stem cells, and act together with chemotherapy to block tumor growth and prolong remission in multiple cancer cell types. Metformin can also inhibit the inflammatory response associated with cellular transformation and cancer stem cell growth. In addition, metformin can accelerate the growth of BRAF V600Edriven melanoma by upregulating VEGF-Aand promote the angiogenic phenotype in the ERalpha negative MDA-MB-435 breast cancer model. Overall, metformin may only have effects in preventing tumor initiation but after the cancer has been established it may not have an effect. Our data also showed that metformin exposure did not inhibit colorectal cancer cell growth, induce apoptosis or autophagy and cell cycle arrest. In agreement with in vitro, in vivo study revealed that metformin did not suppress tumor growth but AMPK activator AICAR emerged antitumor activity. Therefore, metformin might have no antineoplastic activity for CRC cells as a single agent. The anticancer effects of AICAR are mediated by the activation of AMPK and reduction of mTOR signaling. AMPK activation can suppress mTOR pathway to inhibit cell growth and proliferation. AICAR have been reported to enhance the efficacy of conventional chemotherapeutic agents in the treatment of local and metastatic nasopharyngeal carcinoma. AMPK activators such as AICAR provide a therapeutic strategy for hematological malignancies. First, AICAR can induce apoptosis in B-cell chronic lymphocytic leukemia cellsand kill chronic myelogenous leukemiacells through PKC-dependent induction of autophagic cell death. Second, AICAR has antileukemic effects on BCR-ABL-expressing cellsand childhood acute lymphoblastic leukemiacells. Third, AICAR can induce G/S arrest and Nanog downregulation via p53 and enhance erythroid differentiation. Finally, AICAR can also induce apoptosis independently of AMPK and p53 through up-regulation of the BH3-only Benzoylpaeoniflorin proteins BIM and NOXA in chronic lymphocytic leukemia cells. In addition to NPC and leukemia, AICAR is involved in neural stem cell growth suppression and cell cycle arrest by down-regulating phosphoretinoblastoma protein and cyclin D. AICAR can inhibit the growth of retinoblastoma by decreasing angiogenesis and inducing apoptosisor activation of AMPK. AICAR is also demonstrated to inhibit the proliferation of EGFRvIII expressing glioblastoma through AMPK pathway. Moreover, AICAR can be used in clinical trials as a cardioprotectant under ATPdepleted conditions and has been shown to be an exercise mimetic in animals. In agreement with these results, we reported that AICAR can induce apoptosis to emerge antineoplastic activity. Furthermore, AICAR enhanced the cytotoxic effect of 5-FU through AMPK activation. In conclusion, our study revealed that use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR can induce apoptosis and emerge antineoplastic activity. Furthermore, activation of AMPK might be a key cause that AICAR can enhance the cytotoxic effect of 5FU in colorectal cancer cells. The study of adipose tissue biology is becoming Praeruptorin-B increasingly important as obesity and its related comorbidities, including type 2 diabetes, cardiovascular disease and certain cancers, are threatening the health of a growing number of people worldwide.