D-Limonene and its metabolites, perillic acid, dihydroperillic acid, uroterpenol, and limonene1,2-diol, may inhibit tumor growth via inhibition of p21-dependent signaling and apoptosis resulting from induction of the transforming growth factor beta-signaling pathway (9) (10). D-Limonene metabolites also cause G1 cell cycle arrest, inhibit post-translational modification of signal transduction proteins, and cause differential expression of cell cycle- and apoptosis-related genes (6).
D-limonene induces apoptosis via the mitochondrial death pathway and suppression of the PI3K/Akt pathway in human colon cancer cells (16).
Animal studies show activity of D-limonene against pancreatic, stomach, colon, skin, and liver cancers (5) (17). Data also indicate that D-limonene slows the promotion/progression stage of carcinogen-induced tumors in rats (11) (12).
The chemopreventive activity of D-limonene may be via inhibition of inflammation, oxidative stress and Ras-signaling as well as the induction of pro-apoptotic state in a mouse model of skin tumorigenesis (18).