Apo-10′-lycopenoic acid inhibits cancer cell migration and angiogenesis and induces peroxisome proliferator-activated receptor γ

Scope: We have previously shown that apo-10'-lycopenoic acid (ALA), a derivative of lycopene through cleavage by carotene-9',10'-oxygenase, inhibits tumor progression and metastasis in both liver and lung cancer animal models. The underlying mechanism remains unknown. We hypothesized that ALA inhibits cancer cell motility and angiogenesis by up-regulating peroxisome proliferator-activated receptor gamma (PPAR gamma) which is involved in controlling angiogenesis, tumor progression and metastasis. Methods and results: ALA treatment, in dose-dependent manner, was effective at inhibiting migration and invasion of liver and lung cancer cells (HuH7 and A549) in both Transwell and wound-healing models, as well as suppressing actin remodeling and ruffling/lamellipodia formation in HuH7 and immortalized lung BEAS-2B cells. ALA treatment resulted in suppression of angiogenesis in both tube formation and aortic ring assays and inhibition of matrix metalloproteinase-2 expression and activation in both HuH7 and A549 cells. Additionally, ALA dose-dependently increased the mRNA expression and protein levels of PPAR gamma in human THLE-2 liver cells. Conclusion: ALA inhibits cancer cell motility and angiogenesis and induces PPAR gamma expression, which could be one of the potential mechanisms for ALA protecting against tumor progression. (C) 2018 Elsevier Inc. All rights reserved.