Apo‐10′‐Lycopenoic acid Inhibits Cancer Cell Migration and Angiogenesis by Suppressing Lamellipodia Formation

Abstract

Epidemiologic studies have shown that an increase in the dietary intake of tomato and tomato‐based products or higher blood levels of lycopene, is associated with a reduced risk of cancer. Apolycopenoids can be produced by either lycopene cleavage through carotenoid cleavage enzymes, such as beta‐carotene 9′,10′‐oxygenase or the consumption of tomato and tomato products, such as tomato juice. We have previously shown that apo‐10′‐lycopenoic acid, a relative stable derivative of apo‐10′‐lycopenoids, could inhibit tumorigenesis in both lung cancer and liver cancer animal models. To further elucidate the potential mechanisms for the chemopreventive effect of apo‐10′‐lycopenoic acid against cancer development, we examined the ability of apo‐10′‐lycopenoic acid on migration of cancer cells (A549 and HuH7 cells) and endothelial cells (HMEC‐1) using cell migration assays, and angiogenesis using endothelial tube formation and aortic ring assays. We demonstrated that apo‐10′‐lycopenoic acid, in dose‐dependent manner, is effective at inhibiting migration and invasion of both cancer and endothelial cells by suppressing actin remodeling and ruffling/lamellipodia formation. In addition, apo‐10‐lycopenoic acid treatment results in suppression of angiogenesis in both tube formation and aortic ring assays. Apo‐10‐lycopenoic acid also inhibits matrix metalloproteinase‐2 (MMP‐2) expression and activation in A549 cells. Overall, these data demonstrate that apo‐10′‐lycopenoic acid can inhibit cancer cell motility and angiogenesis which could be one of the potential mechanisms for the chemopreventive effect of apo‐10′‐lycopenoic acid against tumorigenesis.Support or Funding InformationSupported by USDA/ARS (58‐1950‐0014)