Junrui Cheng1, Benchun Miao1, Kang-Quan Hu1, Xueyan Fu1, Xiang-Dong Wang2. 1. Nutrition and Cancer Biology Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. 2. Nutrition and Cancer Biology Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. Electronic address: xiang-dong.wang@tufts.edu.
Abstract
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 γ (PPARγ) 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 PPARγ in human THLE-2 liver cells. CONCLUSION: ALA inhibits cancer cell motility and angiogenesis and induces PPARγ expression, which could be one of the potential mechanisms for ALA protecting against tumor progression.
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 γ (PPARγ) 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 PPARγ in human THLE-2 liver cells. CONCLUSION:ALA inhibits cancer cell motility and angiogenesis and induces PPARγ expression, which could be one of the potential mechanisms for ALA protecting against tumor progression.
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