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

Authors: CHENG, JUNRUI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MIAO, BENCHUN - Tufts University; HU, KANG-QUAN - Tufts University; FU, XUEYAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WANG, XIANG-DONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/11/2018
Publication Date: 2/16/2018
Citation: Cheng, J., Miao, B., Hu, K., Fu, X., Wang, X. 2018. Apo-10'-lycopenoic acid inhibits cancer cell migration and angiogenesis and induces peroxisome proliferator-activated receptor gamma. Journal of Nutritional Biochemistry. 56:26-34. https://doi.org/10.1016/j.jnutbio.2018.01.003.
DOI: https://doi.org/10.1016/j.jnutbio.2018.01.003

Interpretive Summary: We have previously shown that apo-10'-lycopenoic acid, a derivative of lycopene through cleavage by carotenoid cleavage enzyme, inhibits tumor progression and metastasis in both liver and lung cancer animal models. In the present study, we present evidence that apo-10'-lycopenoic acid, is effective at inhibiting angiogenesis, migration and invasion of human cancer cells. Additionally, apo-10'-lycopenoic acid functions as a natural activator to a cell nuclear receptor (called peroxisome proliferator-activated receptor-gamma), which is involved in controlling angiogenesis, tumor progression and metastasis. In conclusion, apo-10'-lycopenoic acid inhibits cancer cell motility and angiogenesis, which could be one of the potential mechanisms for apo-10'-lycopenoic acid protecting against tumor progression.

Technical 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 gamma (PPARgamma) 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 PPARgamma in human THLE-2 liver cells. Conclusion: ALA inhibits cancer cell motility and angiogenesis and induces PPARgamnma expression, which could be one of the potential mechanisms for ALA protecting against tumor progression.