Xanthophyll β‐Cryptoxanthin Inhibits Highly Refined Carbohydrate Diet–Promoted Hepatocellular Carcinoma Progression in Mice

Lim, Ji Ye; Li, Chun; Hu, Kang‐Quan; Smith, Donald E.; Wu, Dayong; Lamon‐Fava, Stefania; Ausman, Lynne M.; Wang, Xiangdong

doi:10.1002/mnfr.201900949

Cited by 15 publications

(15 citation statements)

References 54 publications

(58 reference statements)

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“…Since apo-carotenoid, metabolites of BCO2 can be further cleaved by BCO1 to generating vitamin A (30), our findings suggest that BCX itself exerted a protective effect. This is corroborated by our recent study with BCX supplementation in fatty liver and hepatocellular carcinoma in mice, in which BCX was effective in preventing those outcomes (12,15,16,31). By contrast, in the study by Amengual et al (17), severe liver steatosis was developed in BCO2-KO mice at ~3 months (13 weeks) of age after feeding a vitamin A-deficient purified diet (based on AIN-93G formulation) supplemented with 50 mg/kg lutein or 50 mg/kg zeaxanthin.…”

Section: Discussionsupporting

confidence: 78%

“…Second, the mean liver BCX concentration in the mice supplemented with 10 mg BCX/kg diet in this study (0.64 nmol/g) was comparable to that reported in human livers (0.66 nmol/g) (34). Furthermore, the BCX dose used in the present study, which was equivalent to daily human consumption of 0.87 mg of BCX, can be obtained from dietary citrus fruits, such as consuming three raw tangerines daily (15,16,31).…”

Section: Discussionsupporting

confidence: 77%

“…The exact mechanism of this protective effect is unclear, since BCX can be cleaved by BCO1 and BCO2, suggesting a multifaceted biological action. A recent study from our laboratory suggested that the BCX inhibits inflammation and liver tumor development independent of BCO1/ BCO2 (15,16).…”

Section: Introductionmentioning

confidence: 97%

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Xanthophyll β-cryptoxanthin treatment inhibits hepatic steatosis without altering vitamin A status in β-carotene 9',10'-oxygenase knockout mice

Liu¹,

Rafacho²,

Wang³

2022

Hepatobiliary Surg Nutr

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Background: β-cryptoxanthin (BCX), one of the major carotenoids detected in human circulation, can protect against the development of fatty liver disease. BCX can be metabolized through β-carotene-15,15'oxygenase (BCO1) and β-carotene-9',10'-oxygenase (BCO2) cleavage pathways to produce both vitamin A and apo-carotenoids, respectively, which are considered important signaling molecules in a variety of biological processes. Recently, we have demonstrated that BCX treatment reduced hepatic steatosis severity and hepatic total cholesterol levels in both wide type and BCO1 -/-/BCO2 -/double knock out (KO) mice.Whether the protective effect of BCX is seen in single BCO2 -/-KO mice is unclear.Methods: In the present study, male BCO2 -/-KO mice at 1 and 5 months of age were assigned to two groups by age and weight-matching as follows: (I) -BCX control diet alone (AIN-93 purified diets); (II) +BCX 10 mg (supplemented with 10 mg of BCX/kg of diet) for 3 months. At 4 and 8 months of age, hepatic steatosis and inflammatory foci were evaluated by histopathology. Retinoids and BCX concentrations in liver tissue were analyzed by HPLC. Hepatic protein expressions of SIRT1, acetylated and total FoxO1, PGC1α, and PPARα were determined by the Western blot analysis. Real-time PCR for gene expressions (MCAD, SCD1, FAS, TNFα, and IL-1β gene expression relative to β-actin) was conducted in the liver.Results: Steatosis was detected at 8 months but not at 4 months of age. Moreover, BCX supplementation significantly reduced the severity of steatosis in the livers of BCO2 KO mice, which was associated with changes in hepatic SIRT1 acetylation of FOXO1, PGC1α protein expression and PPARα protein expression in BCO2 -/-KO mice. HPLC analysis showed that hepatic BCX was detected in BCX supplemented groups, but there were no differences in the hepatic levels of retinol and retinyl palmitate (RP) among all groups.Conclusions: The present study provided experimental evidence that BCX intervention can reduce liver steatosis independent of BCO2.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 77%

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Xanthophyll β-cryptoxanthin treatment inhibits hepatic steatosis without altering vitamin A status in β-carotene 9',10'-oxygenase knockout mice

Liu¹,

Rafacho²,

Wang³

2022

Hepatobiliary Surg Nutr

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“…It is mostly present in citrus fruits, although it is also found in corn, peas, and other yellow animal products (16,39). β-cryptoxanthin has been demonstrated in animal experiments to have preventative and inhibitory effects on a number of malignancies, including colon cancer (40), gastric cancer (41), lung cancer (42)(43)(44), bladder cancer (45), and liver cancer (46) through a variety of molecular mechanisms. It has been demonstrated that β-cryptoxanthin in combination with oxaliplatin dramatically increased the apoptosis of colon cancer cells in vitro and in vivo, indicating anti-tumor and therapeutic actions on CRC (40).…”

Section: Discussionmentioning

confidence: 99%

Association of Retinol and Carotenoids Content in Diet and Serum With Risk for Colorectal Cancer: A Meta-Analysis

et al. 2022

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BackgroundColorectal cancer (CRC) risk is linked to serum and dietary retinol and carotenoids, according to clinical and epidemiological research. However, the findings are not consistent. As a result, we did this meta-analysis to determine the link between them.MethodsFrom 2000 through 2022, the PubMed, Web of Science, and Embase databases, as well as pertinent article references, were searched and filtered based on inclusion and exclusion criteria and literature quality ratings. High and low intake were used as controls, and OR (odds ratio) or RR (relative risk) and 95% confidence interval were extracted. The extracted data were plotted and analyzed using Stata12.0 software.ResultsA total of 22 relevant studies were included, including 18 studies related to diet and 4 studies related to serum. For high and low intake or concentration controls, the pooled OR was as follows: β-carotene (OR = 0.89, 95% CI: 0.78–1.03), α-carotene (OR = 0.87, 95% CI: 0.72–1.03), lycopene (OR = 0.93, 95% CI: 0.81–1.07), lutein/zeaxanthin (OR = 0.96, 95% CI: 0.87–1.07), β-cryptoxanthin (OR = 0.70, 95% CI: 0.48–1.01), total carotenoids (OR = 0.97, 95% CI: 0.81–1.15), retinol (OR = 0.99, 95% CI: 0.89–1.10), serum carotenoids (OR = 0.73, 95% CI: 0.58–0.93), serum retinol (OR = 0.62, 95% CI: 0.26–1.49). Subgroup analysis was performed according to tumor type, study type and sex.ConclusionTotal carotenoid intake and Lutein/Zeaxanthin intake were not associated with CRC risk. High β-carotene, α-carotene, lycopene, and β-cryptoxanthin all tended to reduce CRC risk. Serum carotenoid concentrations were significantly inversely associated with CRC risk.

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“…Another paper demonstrated that dietary BCX for 24 weeks suppressed the progression of chemically and highly refined carbohydrate diet-induced hepatocellular carcinoma in mice. The mechanisms underlying this effect involved an increase in p53 acetylation, with the subsequent induction of apoptosis and the reduction in HIF-1α and its down-stream targets, MMP-2 and MMP-9 [370].…”

Section: In Vivo Studiesmentioning

confidence: 99%

Anti-Inflammatory and Anticancer Effects of Microalgal Carotenoids

et al. 2021

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Acute inflammation is a key component of the immune system’s response to pathogens, toxic agents, or tissue injury, involving the stimulation of defense mechanisms aimed to removing pathogenic factors and restoring tissue homeostasis. However, uncontrolled acute inflammatory response may lead to chronic inflammation, which is involved in the development of many diseases, including cancer. Nowadays, the need to find new potential therapeutic compounds has raised the worldwide scientific interest to study the marine environment. Specifically, microalgae are considered rich sources of bioactive molecules, such as carotenoids, which are natural isoprenoid pigments with important beneficial effects for health due to their biological activities. Carotenoids are essential nutrients for mammals, but they are unable to synthesize them; instead, a dietary intake of these compounds is required. Carotenoids are classified as carotenes (hydrocarbon carotenoids), such as α- and β-carotene, and xanthophylls (oxygenate derivatives) including zeaxanthin, astaxanthin, fucoxanthin, lutein, α- and β-cryptoxanthin, and canthaxanthin. This review summarizes the present up-to-date knowledge of the anti-inflammatory and anticancer activities of microalgal carotenoids both in vitro and in vivo, as well as the latest status of human studies for their potential use in prevention and treatment of inflammatory diseases and cancer.

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Xanthophyll β‐Cryptoxanthin Inhibits Highly Refined Carbohydrate Diet–Promoted Hepatocellular Carcinoma Progression in Mice

Cited by 15 publications

References 54 publications

Xanthophyll β-cryptoxanthin treatment inhibits hepatic steatosis without altering vitamin A status in β-carotene 9',10'-oxygenase knockout mice

Xanthophyll β-cryptoxanthin treatment inhibits hepatic steatosis without altering vitamin A status in β-carotene 9',10'-oxygenase knockout mice

Association of Retinol and Carotenoids Content in Diet and Serum With Risk for Colorectal Cancer: A Meta-Analysis

Anti-Inflammatory and Anticancer Effects of Microalgal Carotenoids

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