Background:Globally Esophageal cancer is a common cancer arising from human esophageal mucosal tissue. Epidemiological studies suggest inverse correlation between carotenoid intake and incident risk of this devastating malignancy.Methods:In an effort to examine the modulatory role of carotenoids in human esophageal carcinogenesis at a cellular level, we examined the effects of α-carotene and β-carotenes, on cell proliferation and DNA synthesis in human esophageal epithelial (HEE) cells and human esophageal squamous cancer (HESC) cells in in-vitro cultures. HEE and HESC cells were incubated with different concentrations of α- and β-carotenes both individually and in combination.Results:Both Carotenes significantly inhibited (p<0.05) cellular proliferation and decreased DNA synthesis in HEE and HESC cells. The effect of α- and β-carotene together on DNA synthesis in HEE and HESC cells was significantly greater than either carotenoid alone, suggesting a synergistic effect. Greater magnitude of cellular inhibition of DNA synthesis was observed on HEE cells than HESC cells.Conclusion:Our results suggest that a combination of α-and β-carotene may provide a novel strategy for prevention and treatment of esophageal and upper aero digestive tract cancer in humans.