AbstractEvidence from epidemiologic studies has shown that diets rich in fruit and vegetables are associated with reduced risk of chronic and degenerative diseases. Plants contain phytochemicals, which are believed to account for some of the positive effects through interactions with protein kinases.The present work is a screening of dietary phytochemicals for their ability to modulate the activity of the intracellular protein kinase A (PKA) using a novel PKA-sensitive luciferase. Some of the extracts of dietary plants and spices found to inhibit PKA-activity were closer examined with respect to their ability to reduce intracellular cyclic AMP (cAMP) levels. HepG2-cells transfected with a luciferase reporter for PKA and mAS-cells isolated from transgenic mice were used. Clove and cinnamon phytochemicals inhibited PKA in a dose-dependent manner at low, non-toxic concentrations in HepG2-cells. Allspice phytochemicals inhibited PKA in a dose-dependent manner in both HepG2-and mAS-cells, and this extract was found to be non-cytotoxic. The three spice extracts led to a dose-dependent reduction in intracellular cAMP, which may explain the results. Green Tea phytochemicals at the lowest, non-toxic concentration was found to inhibit PKA-activity, and the mechanism seems to be reduction in intracellular levels of cAMP. Crowberry and walnut phytochemicals inhibited PKA-activity in a dose-dependent manner in HepG2-cells, which may be explained by reduced levels of intracellular cAMP. Walnut was the only plant extract found to have PKA-inhibitory effects in mAS-cells.Clove, Green Tea and walnut phytochemicals were found to inhibit the luciferase enzyme dose-dependently, suggesting that the inhibitory effects on PKA are higher than observed here.