Beta-Carotene

Biochem Biophys Res Commun. 1997 Apr 28;233(3):658-62.

Hypocholesterolemic effect of lycopene and beta-carotene is related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophages.[Pubmed: 9168909 ]

Beta-Carotene and lycopene are derived from plants, and they share similar initial synthetic pathway with cholesterol, which is synthesized in animal but not in plant cells. Thus, we sought to analyze the effect of carotenoids on macrophage cholesterol metabolism, in comparison to the effect of LDL cholesterol and of the cholesterol synthesis inhibitor, fluvastatin. In J-774 A. 1 macrophage cell line, the cellular cholesterol synthesis from [3H]-acetate, but not from [14C] mevalonate, was suppressed by 63% any by 73% following cell incubation with Beta-Carotene or lycopene (10 microM) respectively, in comparison to a 90% and 91% inhibition by LDL (100 micrograms of cholesterol), or by fluvastatin (10 micrograms/ml) respectively. However, unlike LDL derived cholesterol, which also suppresses macrophage LDL receptor activity, lycopene and Beta-Carotene augmented the activity of the macrophage LDL receptor, similarly to the effect of fluvasfatin. In agreement with these in vitro observations, dietary supplementation of tomato's lycopene (60 mg/day) to 6 males for a 3 months period resulted in a significant 14% reduction in their plasma LDL cholesterol concentrations.
CONCLUSIONS:
We thus conclude that dietary supplementation of carotenoids may act as moderate hypocholesterolemic agents, secondary to their inhibitory effect on macrophage 3-hydroxy-3-methyl glutaryl coenzyme A (HMGCoA) reductase, the rate limiting enzyme in cholesterol synthesis.

J Nutr Biochem. 2014 Jun;25(6):655-64.

β-Carotene inhibits neuroblastoma cell invasion and metastasis in vitro and in vivo by decreasing level of hypoxia-inducible factor-1α.[Pubmed: 24746828]

While Beta-Carotene is a vitamin A precursor that has been shown to exert antioxidant and anticancer effects, the anti-metastatic effects of Beta-Carotene on neuroblastoma cells remain poorly understood. The aim of the present study was to investigate the anti-metastatic effects of Beta-Carotene on highly malignant SK-N-BE(2)C neuroblastoma cells in vitro and in vivo.
METHODS AND RESULTS:
Treatment of SK-N-BE(2)C cells with Beta-Carotene was found to attenuate the migratory and invasive capabilities of the cells. In addition, the enzymatic activity and expression of matrix metalloproteinase (MMP)-2 was suppressed following Beta-Carotene treatment under both normoxia and hypoxia. To induce metastasis, immunodeficient nude mice were injected with SK-N-BE(2)C cells via the tail vein in vivo. The incidence of liver metastasis and mean tumor volume in mice that were administered Beta-Carotene was decreased compared to controls. Furthermore, mRNA levels of MMPs, membrane-type (MT) 2 MMP and tissue inhibitors of metalloproteinases in liver tumor tissues were also lower following Beta-Carotene treatment. Level of hypoxia-inducible factor-1α (HIF-1α) and its downstream targets, vascular endothelial growth factor and glucose transporter 1 (GLUT1), were lower both in vitro and in vivo following Beta-Carotene treatment.
CONCLUSIONS:
In conclusion, the present study provides the first evidence that Beta-Carotene may represent an effective chemotherapeutic agent by regulating the invasion and metastasis of neuroblastoma via HIF-1α.

Mutat Res. 1993 Nov;303(3):109-12.

Protective effects of chlorogenic acid, curcumin and beta-carotene against gamma-radiation-induced in vivo chromosomal damage.[Pubmed: 7694126]

The mouse bone marrow micronucleus test was carried out to evaluate the possible role of the dietary constituents chlorogenic acid (CGA), curcumin (CR) and Beta-Carotene (BC) in modulating the in vivo chromosomal damage induced by gamma-radiation.
METHODS AND RESULTS:
The results obtained suggest that oral administration of CGA (50, 100 and 200 mg/kg b.w.), CR (5, 10 and 20 mg/kg b.w.) and BC (0.5 and 2.5 mg/kg b.w.) to mice can significantly reduce the frequencies of micronucleated polychromatic erythrocytes (Mn PCEs) induced by whole body exposure to gamma-radiation (1.15 Gy; 0.05 Gy/s). With CGA and CR, this effect was observed after a single administration either 2 h before or immediately after irradiation. However, with BC a 7-day feeding before irradiation was necessary to obtain a significant reduction in the incidence of Mn PCEs.
CONCLUSIONS:
The protective effects of CGA, CR and BC were observed in bone marrow cells sampled 24, 30 and 48 h after exposure to radiation.

Mar-Apr 2018;32(2):255-264.

Anti-inflammatory Activity of β-Carotene, Lycopene and Tri- n-butylborane, a Scavenger of Reactive Oxygen Species[Pubmed: 29475907]

Abstract Background/aim: The polyene carotenoids β-carotene and lycopene are antioxidants that not only quench singlet oxygen but also inhibit lipid peroxidation. Tri-n-butyl borane (TBB) is used as an initiator for dental resin materials and is extremely reactive with oxygen and reactive oxygen species (ROS). This reactionability of TBB may be analogous to that of carotenoids with ROS. To clarify the biological activity of such ROS scavengers, we investigated the anti-inflammatory activity of β-carotene, lycopene and TBB in terms of the expression of RNA for lipopolysaccharide (LPS)-induced cyclooxygenase-2 (Cox2), nitric oxide synthase 2 (Nos2) and tumor necrosis factor-alpha (Tnfa), and mRNA expression and up-regulation of heme oxygenase 1 (Hmox1) mRNA in RAW264.7 cells. Materials and methods: mRNA expression was investigated using real-time reverse transcriptase-polymerase chain reaction (PCR). The antioxidant activity of carotenoids was evaluated using the induction period method in the azobisisobutyronitrile or benzoyl peroxide-methyl methacrylate system. Results: Hmox1 mRNA, but not Cox2 and Nos2 mRNA, was up-regulated by 100 μM β-carotene and lycopene, and by 0.125% TBB. LPS-stimulated Cox2, Nos2 and Tnfa gene expression was inhibited by 50 μM β-carotene and lycopene, and by 0.5-1% TBB. Both β-carotene and lycopene had weak antioxidant activity, but β-carotene showed pro-oxidant activity at higher concentrations. Conclusion: The anti-inflammatory activity of β-carotene, lycopene and TBB may be related to their ROS-scavenging activity. Additionally, the activity of carotenoids and TBB may be attributed to the electrophilicity of ROS-induced carotenoid intermediates and boranes, respectively. Their anti-inflammatory activity may be attributable to enhancement of the potency of the electrophile/antioxidant response element transcription system in view of their up-regulation of Hmox1 mRNA expression. Keywords: COX2; HMOX1; LPS; NOS2; RAW264.7 cells; lycopene; tri-n-butyl borane; β-Carotene.

Cancer Lett. 1992 Apr 15;63(2):125-33.

Inhibitory effect of conjugated dienoic derivatives of linoleic acid and beta-carotene on the in vitro growth of human cancer cells.[Pubmed: 1562989]

The effects of physiologic concentrations of conjugated linoleic acid (CLA) and Beta-Carotene were assessed on human (M21-HPB, malignant melanoma; HT-29, colorectal; MCF-7, breast) cancer cells.
METHODS AND RESULTS:
The incubation of cancer cells with CLA showed significant reductions in proliferation (18-100%) compared to control cultures. M21-HPB and MCF-7 cell mortality was dose- and time-dependent. Beta-Carotene was inhibitory to breast cells only. MCF-7 cells supplemented with CLA incorporated significantly less [3H]leucine (45%), [3H]uridine (63%) and [3H]thymidine (46%) than control cultures. M21-HPB and HT-29 cells supplemented with CLA incorporated less [3H]leucine (25-30%).
CONCLUSIONS:
These in vitro results suggest that CLA and Beta-Carotene may be cytotoxic to human cancer cells in vivo.

Fertil Steril. 2009 Dec;92(6):2028-33.

Antiapoptotic and antioxidant effects of beta-carotene against methotrexate-induced testicular injury.[Pubmed: 19046577]

In each group, 100 tubules were classified as intact, sloughing, atrophic, and degenerated. Caspase-3, a universal effector of apoptosis, was evaluated according to staining in place of coloring as weak, mild, and strong. RESULT(S): To investigate the effect of Beta-Carotene against testicular injury induced by methotrexate (MTX).
METHODS AND RESULTS:
Twenty-eight rats were separated into four groups: control, Beta-Carotene, MTX, and Beta-Carotene + MTX. At the end of the treatment, the animals were killed, and tissue samples were examined via histologic and biochemical methods. In each group, 100 tubules were classified as intact, sloughing, atrophic, and degenerated. Caspase-3, a universal effector of apoptosis, was evaluated according to staining in place of coloring as weak, mild, and strong. In the MTX group, 58.5 + 3.7% of tubules were sloughing, 10.8 + 2.1% of tubules were atrophic, and 2.0 + 0.6% of tubules were degenerative. In the Beta-Carotene + MTX group, the affected tubule number was statistically significantly lower than in the MTX group. The distribution of caspase-3 in the MTX group showed a statistically significant increase, but it decreased in the Beta-Carotene + MTX group. The enzyme activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GP-x) and the level of malondialdehyde (MDA) increased and decreased in parallel.
CONCLUSIONS:
Our results indicate that Beta-Carotene may be useful in decreasing the side effects of chemotherapy, including apoptotic cell death.

J Food Sci. 2014 Sep;79(9):C1688-94.

β-Carotene as a membrane antioxidant probed by cholesterol-anchored daidzein.[Pubmed: 25103027]

METHODS AND RESULTS:
Beta-Carotene is found to be more effective as an antioxidant in phosphatidylcholine (PC) liposomes when protecting against hydrophilic radicals compared to lipophilic radicals, as measured by the rate of formation of conjugated dienes. Daidzein alone is without effect, but decreases the antioxidative effect of Beta-Carotene for hydrophilic initiation and increases the effect for lipophilic initiation. The newly synthesized 7-cholesterylglycol daidzein has the opposite effect for Beta-Carotene as antioxidant, with a strong enhancement for hydrophilic initiation and a slight decrease for lipophilic initiation.
CONCLUSIONS:
Redistributing Beta-Carotene to membrane surfaces by cholesterol-anchoring of daidzein enhances protection against aqueous radicals significantly at the expense of protection against lipid-derived radicals.