Introduction: Pancreatic cancer continues to have a poor prognosis despite resection and adjuvant therapy. As tumor cells outgrow their blood supply, hypoxia induces an increase in anaerobic metabolism, glucose uptake and the expression of the facilitative glucose transporter, GLUT-1. GLUT-1 is up-regulated in many cancers and is induced by the transcription factor hypoxia-inducible factor-1 (HIF-1). Apigenin is a plant flavonoid with anti-proliferative effects in pancreatic cancer cells and has been shown to inhibit HIF-1 expression. We hypothesized that apigenin inhibits pancreatic cancer cell proliferation via down-regulation of the GLUT-1 glucose transporter and thus decreases glucose uptake. Materials and Methods: Immunohistochemistry with anti-GLUT-1 antibody was used to quantify expression in 15 human pancreatic tumor and respective control tissue samples using a grading system of: 0 none, 1+ weak and 2+ strong staining. DNA synthesis was measured in CD18 human pancreatic cancer cells after treament with a non-metabolized glucose analogue (D-Mannoheptulose) to demonstrate glucose dependent-growth. Viable cell counts were performed on two pancreatic cancer cell lines (CD18 and S2-103) that were treated with apigenin (6.25-100 µM) to evaluate cell proliferation. Real time RT- PCR was performed on CD18 and S2-013 pancreatic cancer cells treated with apigenin (0-50 µM) to evaluate concentration dependent GLUT-1 expression. C14-2-deoxyglucose uptake was measured in CD18 and S2-013 pancreatic cancer cells treated with apigenin (0-100 µM) versus control. Results: GLUT-1 expression was significantly increased in human pancreatic tumor samples versus controls (2+ strong staining in 15/15 of the tumor samples versus 0/15 with 2+ strong staining and 2/15 with 1+ weak staining in controls (P<0.001). D-Mannoheptulose inhibited both basal and insulin-stimulated DNA synthesis in CD18 pancreatic cancer cells (P<0.01, control vs D-Mannoheptalose; P<0.01, insulin vs insulin+D-Mannoheptulose) in parallel with inhibition of basal and insulin-stimulated glucose uptake. In CD18 and S2-013 human pancreatic cancer cells, apigenin significanlty inhibited cell growth (48 and 72 hours; P<0.001) and down-regulated GLUT-1 expression (6.25-100µM, P<0.05). Apigenin (50µM) decreased C14-2-deoxyglucose uptake in CD18 and S2-013 pancreatic cancer cells compared to control. Conclusions: Apigenin induces growth inhibition in human pancreatic cancer cells, which are dependent on glucose for proliferation. One of the mechanisms of apigenin-mediated anti-proliferative activity may be via down-regulation of GLUT-1 expression and in turn decreased glucose uptake and metabolism.