A recent report showed that gluconeogenesis was down-regulated in hepatocellular carcinoma and the reduced gluconeogenesis may facilitate tumorigenesis by accumulation of glucose 6-phosphate, the precursor for nucleotide synthesis. The expression profile of proteomes in control and citreoviridintreated tumors provides novel implications for understanding the antitumorigenic effect by activation of gluconeogenesis in cancer cells. First, the glucose synthesized could be converted into myoinositol, which has anti-cancer activity. We observed the upregulation of the enzyme IPS 1 with treatment of citreoviridin. This enzyme catalyzes the key rate-limiting step in the myo-inositol biosynthesis pathway. The level of myo-inositol was found to be higher in normal tissue compared to Perifosine breast cancer tissue but lower in lung tumors. Besides, myo-inositol was shown to have anti-cancer activity by inhibiting tumor formation of colon, mammary, soft tissue and lung cancers. The phosphorylated myo-inositol, inositol hexaphosphate was also recognized for its effectiveness in cancer prevention. IP6 is able to induce G1 cell cycle arrest by modulating cyclins, CDKs, p27Kip1, p21CIP1/WAF1, and pRb in prostate cancer and breast cancer. With the treatment of citreoviridin, the glucose synthesized from gluconeogenesis may also be converted to other LY2109761 compounds and escape from utilization by glycolysis. The reduction in glycolysis flux results in the decrease of glycolytic intermediates to sustain the continuous building blocks for macromolecular synthesis and thereby inhibits the proliferation of cancer cells. We found that the expression level of aldose reductase that converts glucose to sorbitol was higher in citreoviridin-treated tumors. The increased intracellular glucose results in its conversion to sorbitol. Although sorbitol entering the polyol pathway can be converted to fructose by sorbitol dehydrogenase, high glucose levels still favors the production of sorbitol. Glucose synthesized from gluconeogenesis may also be polymerized into glycogen for storage. Thus, the decrease of glucose influx into glycolysis inhibits proliferation of cancer cells. A previous report showed that the expression level of UDPGP, activities of phosphoglucomutase and glycogen synthase were all decreased in tumor tissues, so the defective glycogen synthesis process is unable to compete with glycolysis. In our proteomic profiling data, we observed that the expression levels of PGM and UDPGP were higher with citreoviridin treatment in lung cancer. Regarding glycogen breakdown, previous studies suggested that glycogen phosphorylase was expressed in tumor tissues and served as a target for anticancer therapy.