Antimetastatic Effects and Mechanisms of Apo-8′-Lycopenal, an Enzymatic Metabolite of Lycopene, Against Human Hepatocarcinoma SK-Hep-1 Cells

Yang, Chang‐Hsien; Hu, Te-Yu; Hu, Miao‐Lin

doi:10.1080/01635581.2012.643273

Cited by 32 publications

(21 citation statements)

References 51 publications

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“…Thus, this pattern suggests that lycopene cleavage metabolites produced by BCO2 may have anti-prostate-cancer bioactivity and that their production is diminished in the Bco2−/− mice. Previous studies on the effect of the lycopene metabolite, apo-10’-lycopenoic acid, have shown it to reduce hepatic inflammation, steatosis, and tumorigenesis in mice (60, 61), and other studies of apo-8’-lycopenal in models of liver cancer have been indicative of bioactivity (38, 39), increasing the plausibility of lycopene metabolite activity in the prostate. We also demonstrate that tomato-fed Bco2−/− accumulate lycopene precursors, phytofluene, zeta-carotene, and a suggestion for phytoene, opening the door for hypotheses regarding the potential for BCO2 to cleave additional carotenoids.…”

Section: Discussionmentioning

confidence: 99%

β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model

Tan

Thomas‐Ahner

Moran

et al. 2017

Cancer Prevention Research

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The hypothesis that dietary tomato consumption or the intake of the carotenoid lycopene inhibits prostate cancer arose from epidemiologic studies and is supported by preclinical rodent experiments and in vitro mechanistic studies. We hypothesize that variation in activity of carotenoid cleavage enzymes, such as β-carotene 9’,10’-oxygenase (BCO2), may alter the impact of dietary tomato and lycopene on prostate carcinogenesis and therefore examined this relationship in the TRAMP model. Starting at three weeks of age, TRAMP:Bco2+/+ and TRAMP:Bco2−/− mice were fed either AIN-93G control, or semi-purified diets containing 10% tomato powder or 0.25% lycopene beadlets until 18 weeks of age. Both tomato- and lycopene-fed TRAMP:Bco2−/− mice had significantly greater serum concentrations of total, 5-cis, other cis, and all-trans lycopene than TRAMP:Bco2+/+ mice. Tomato- and lycopene-fed mice had a lower incidence of prostate cancer compared to the control-fed mice. While Bco2 genotype alone did not significantly change prostate cancer outcome in the control AIN-93G-fed mice, the abilities of lycopene and tomato feeding to inhibit prostate carcinogenesis were significantly attenuated by the loss of Bco2 (interaction p=0.0004 and p=0.0383, respectively). Overall, dietary tomato and lycopene inhibited the progression of prostate cancer in TRAMP in a Bco2 genotype-specific manner, potentially implicating the anticancer activity of lycopene cleavage products. This study suggests that genetic variables impacting carotenoid metabolism and accumulation can impact anti-cancer activity and that future efforts devoted to understanding the interface between tomato carotenoid intake, host genetics, and metabolism will be necessary to clearly elucidate their interactive roles in human prostate carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model

Tan

Thomas‐Ahner

Moran

et al. 2017

Cancer Prevention Research

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“…These effects of lycopene were associated with the inhibition of tumour invasion (decreased MMP-9 and upregulated nm23-H1), cell proliferation (decreased PCNA), and angiogenesis (decreased MMP-9 and VEGF, but increased IL-2) in the lungs of nude mice. In SK-Hep-1 cells, apo-8′-lycopene has been shown to exhibit more robust antimetastatic activity than lycopene by inhibiting MMP-2 and MMP-9 expression, increasing the expression of nm23-H1, TIMP-1, and TIMP-2 (MMP tissue inhibitors), suppressing the Monomeric Rho GTPase- and inhibiting the focal adhesion kinase- (FAK-) mediated signalling pathway [100]. Conversely, lycopene has been demonstrated to significantly inhibit the DNA binding of NF- κ B and the simulator protein (SP1) and to thereby decrease MMP-9 secretion and reduce the invasive capacity of human hepatoma cells [101].…”

Section: Potential Mechanisms Of Actions Of Lycopenementioning

confidence: 99%

Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition

Trejo-Solís

Pedraza‐Chaverrí

Torres-Ramos

et al. 2013

Evidence-Based Complementary and Alternative Medicine

118

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Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer. Lycopene, the predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity and has been shown to prevent cancer, as evidenced by clinical trials and studies in cell culture and animal models. In vitro studies have shown that lycopene treatment can selectively arrest cell growth and induce apoptosis in cancer cells without affecting normal cells. In vivo studies have revealed that lycopene treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon. Clinical studies have shown that lycopene protects against prostate cancer. One of the main challenges in cancer prevention is the integration of new molecular findings into clinical practice. Thus, the identification of molecular biomarkers associated with lycopene levels is essential for improving our understanding of the mechanisms underlying its antineoplastic activity.

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“…Recent investigations including our own have proposed that the biological activities of lycopene may be mediated in part by lycopene’s metabolites [193,197,198,199]. As previously mentioned, genetic variants of the BCO2 gene are prevalent in humans and other mammals [184], and BCO2 polymorphism has been associated with modified status of carotenoid and pro-inflammatory cytokine IL-18 [182,184,187,200].…”

Section: Effects Of Tomato and Lycopene Consumption Against Nash Amentioning

confidence: 99%

“…Lycopene metabolite apo-8′-lycopenal has been shown to have similar anti-metastatic effects in SK-Hep-1 cells as lycopene treatments [198], and sharing comparable mechanisms including MMP9 suppression and elevation in TIMP1. However, apo-8′-lycopenal treatment was more effective than lycopene at the same concentration (10 µM) [198].…”

Section: Effects Of Tomato and Lycopene Consumption Against Nash Amentioning

confidence: 99%

Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma: Implications for Lycopene Intervention

Wang

2013

Nutrients

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Increased prevalence of non-alcoholic fatty liver disease (NAFLD) is one of the consequences of the current obesity epidemic. NAFLD is a major form of chronic liver disease that is highly prevalent in obese and overweight adults and children. Nonalcoholic steatohepatitis (NASH) is the severe form of NAFLD, and uncontrolled inflammation as displayed in NASH has been identified as one of the key events in enhancing hepatic carcinogenesis. Lycopene is a non-provitamin A carotenoid and the pigment principally responsible for the characteristic deep-red color of ripe tomato and tomato products, as well as some fruits and vegetables. Lycopene’s innate antioxidant and anti-inflammatory properties have generated research interests on its capacity to protect against human diseases that are associated with oxidative stress and inflammation. In addition, differential mechanisms of lycopene metabolism including endogenous cleavage by carotenoid cleavage oxygenases (BCOs), generate lycopene metabolites that may also have significant impact on human disease development. However, it remains to be elucidated as to whether lycopene or its metabolites apolycopenoids have protective effects against obesity-related complications including inflammation and tumorigenesis. This article summarizes the in vivo experiments that elucidated molecular mechanisms associated with obesity-related hepatic inflammation and carcinogenesis. This review also provides an overview of lycopene metabolism, and the molecular pathways involved in the potential beneficial properties of lycopene and apolycopenoids. More research is clearly needed to fully unravel the importance of BCOs in tomato carotenoid metabolism and the consequence on human health and diseases.

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Antimetastatic Effects and Mechanisms of Apo-8′-Lycopenal, an Enzymatic Metabolite of Lycopene, Against Human Hepatocarcinoma SK-Hep-1 Cells

Cited by 32 publications

References 51 publications

β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model

β-Carotene 9′,10′ Oxygenase Modulates the Anticancer Activity of Dietary Tomato or Lycopene on Prostate Carcinogenesis in the TRAMP Model

Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition

Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma: Implications for Lycopene Intervention

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