In MCF-7 cancer cells, β-carotene increases ROS generation and PPAR-γ expression [3]. The viability of MCF-7 cells was drastically reduced in a dose-dependent manner by β-Carotene (1-100 μM; 72 hours) [3]. In a time-dependent way, β-Carotene (50 μM; 24-72 hours) dramatically increased the levels of PPAR-γ mRNA and protein expression [3]. In a time-dependent way, β-carotene downregulates COX-2, although it increases the amounts of p21 mRNA and protein expression [3]. The percentage of early apoptosis was dramatically raised by β-carotene, and preincubation with GW9662 or GSH mitigated this effect to some extent [3]. Cytochrome C release is induced by beta-carotene [3].

Cell viability assay [5]
Cell Types: MCF-7 Cell
Tested Concentrations: 1 μM, 10 μM, 20 μM, 50 μM, 100 μM
Incubation Duration: 72 hrs (hours)
Experimental Results: The number of viable cells diminished to 70% and 50% respectively at 20°C μM and 50 μM respectively.

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RT-PCR[5]
Cell Types: MCF-7 Cell
Tested Concentrations: 50 μM
Incubation Duration: 24 hrs (hours), 48 hrs (hours), 72 hrs (hours)
Experimental Results: PPAR-γ mRNA upregulation.

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Western Blot Analysis [5]
Cell Types: MCF-7 cells
Tested Concentrations: 50 μM
Incubation Duration: 24 hrs (hours), 48 hrs (hours), 72 hrs (hours)
Experimental Results: PPAR-γ protein expression level was increased.

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Apoptosis analysis [5]
Cell Types: MCF-7 Cell
Tested Concentrations: 50 μM
Incubation Duration: 72 hrs (hours)
Experimental Results: Induced apoptosis of MCF-7 cells.

Absorption, Distribution and Excretion
Following administration of β-carotene, a portion of the administered dose is absorbed unchanged into the circulatory system and stored in adipose tissue. Concomitant administration of β-carotene with a high-fat diet may enhance its absorption. Absorption also depends on the isomer of the molecule, with the cis conformation appearing to have higher bioavailability. The absorption process of β-carotene typically takes 6–7 hours. The AUC reported after oral administration of β-carotene is 26.3 mcg·h/L within 0–440 hours. In dual pharmacokinetic curves, the maximum concentration of β-carotene was reached at 6 hours and 32 hours, respectively, at 0.58 μmol/L. Unabsorbed carotene is excreted in feces. It can also be excreted as a metabolite in feces and urine. Dietary fiber intake can increase the fecal excretion of fats and other fat-soluble compounds, such as β-carotene. Pharmacokinetic studies on the volume of distribution of β-carotene have not yet been conducted.
The clearance rate of orally administered β-carotene is 0.68 nmol/L per hour.
After absorption, carotenoids are transported to the liver via the lymphatic system. They circulate bound to lipoproteins and are present in the liver, adrenal glands, testes, and adipose tissue, and can be converted into vitamin A in various tissues, including the liver. Some β-carotene is absorbed unchanged and circulates bound to lipoproteins; it is obviously allocated to lipids in the body and converted into vitamin A in various tissues, including the liver.
β-carotene absorption depends on the presence of dietary fat and bile in the intestine.
Unconverted β-carotene is present in various tissues, primarily in adipose tissue, adrenal glands, and ovaries. Small amounts of β-carotene are also found in the liver.
The human body absorbs only about one-third of β-carotene or other carotenoids. The absorption of carotenoids is relatively nonspecific and depends on the presence of bile and absorbable fats in the intestine. Steatorrhea, chronic diarrhea, and very low-fat diets significantly reduce their levels. For more complete data on the absorption, distribution, and excretion of β-carotene (9 types), please visit the HSDB record page.

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Metabolism/Metabolites
β-carotene is broken down into retinal by β-carotene dioxygenase in the small intestine and liver mucosa. Retinal is a form of vitamin A. The function of this enzyme is crucial because it determines whether β-carotene is converted into vitamin A or circulates in the blood plasma as β-carotene. Less than a quarter of β-carotene ingested from root vegetables is converted into vitamin A; about half of β-carotene ingested from leafy green vegetables is converted into vitamin A. A portion of β-carotene is converted into retinol in the small intestine wall, primarily through the initial cleavage of its 15,15' double bond to form two retinal molecules. Some retinal is further oxidized to retinoic acid; only half is reduced to retinol, which is then esterified and transported via the lymphatic system. Approximately 20% to 60% of β-carotene is metabolized into retinaldehyde, which is then primarily converted to retinol in the intestinal wall. A small amount of β-carotene is converted into vitamin A in the liver. As long as β-carotene intake is 1-2 times higher than the daily requirement, the conversion rate to vitamin A is inversely proportional to the intake. High doses of β-carotene do not cause abnormally high serum vitamin A concentrations. β-carotene can be converted into two retinaldehyde molecules through the breaking of the 15-15' double bond at the molecular center. Most of the retinaldehyde is reduced to retinol, which then binds to glucuronic acid and is excreted in urine and feces. Some retinaldehyde can be further oxidized to retinoic acid, which can be decarboxylated and further metabolized, secreted into bile, and excreted in feces as glucuronide. There are two main pathways for the conversion of carotenoids into vitamin A in mammals: central cleavage and eccentric cleavage. β-Carotene-15,15'-dioxygenase has been partially purified from the intestines of various animals and has also been found in other organs and species. This enzyme converts β-carotene to two molecules of retinaldehyde in a high yield. Its activity requires molecular oxygen and can be inhibited by thiol-binding and iron-binding agents. Most provitamin A carotenoids, including β-apocaroaldehyde, can be cleaved into retinaldehyde by this enzyme. The maximum activity of this enzyme in rabbits is approximately 200 times that required to meet nutritional needs, but less than 50% of the activity required to produce symptoms of vitamin A poisoning. Eccentric cleavage undoubtedly occurs in plants and certain microorganisms, and may also occur in mammals. However, to date, no carotenoid dioxygenase with eccentric bond specificity has been found in mammals. The yield of β-carotene to β-apocaroaldehyde in vivo and in vitro is very low, and β-apocaroaldehyde is not biosynthesized from β-carotene. The conversion of carotene to retinol is not rapid; therefore, excessive intake of carotene will not lead to vitamin A poisoning. /Carotene/

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Biological Half-Life
The apparent half-life of β-carotene is 6-11 days after the first administration.

Interactions
Smoking is associated with decreased plasma ascorbic acid and β-carotene levels, suggesting that smoking-related chronic inflammation leads to an imbalance in oxidant/antioxidant homeostasis and may increase the risk of oxidative tissue damage and disease. Weaned male Sprague-Dawley rats were paired and fed β-carotene (56.5 mg/L in diet) for 8 weeks, with or without ethanol. As expected, ethanol increased CYP2E1 expression (as determined by Western blot) from 67 ± 8 density units to 317 ± 27 density units (p < 0.001). Furthermore, β-carotene enhanced the ethanol-induced effect, increasing CYP2E1 expression to 442 ± 38 density units (p < 0.01), and a significant interaction existed between the two (p = 0.012). The corresponding enhancement of hydroxylation of p-nitrophenol (a specific substrate of CYP2E1) and the inhibition by diethyl dithiocarbamate (50 μM) confirmed the above-mentioned increases. β-carotene alone also significantly induced CYP4A1 protein expression (328 ± 49 vs. 158 ± 17 density units, p < 0.05). The corresponding CYP4A1 mRNA (measured by Northern blotting) was also increased (p < 0.05), and there was a significant interaction between the two treatments (p = 0.015). The combined use of ethanol and β-carotene had no significant effect on the levels of total cytochrome P-450 or CYP1A1/2, CYP2B, CYP3A, and CYP4A2/3. β-carotene enhanced the induction of CYP2E1 in rat liver by ethanol and increased CYP4A1 expression, which may at least partially explain the associated hepatotoxicity.
Oral administration of aflatoxin B1 (4 mg/kg/day) for 26 consecutive days inhibited the conversion of β-carotene to vitamin A in the intestinal mucosa of rats.
Sulfite-mediated β-carotene destruction was investigated; α-tocopherol, 1,2-dihydroxybenzene-3,5-disulfonic acid, and butylated hydroxytoluene inhibited β-carotene interactions.
For more complete data on β-carotene interactions (25 in total), please visit the HSDB record page.

[1]. Tanumihardjo, S.A., Factors influencing the conversion of carotenoids to retinol: bioavailability to bioconversion to bioefficacy. Int J Vitam Nutr Res, 2002. 72(1): p. 40-5.

[2]. Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr, 1999. 69(6): p. 1071-85.

[3]. beta-Carotene induces apoptosis and up-regulates peroxisome proliferator-activated receptor gamma expression and reactive oxygen species production in MCF-7 cancer cells. Eur J Cancer. 2007 Nov;43(17):2590-601.

[4]. Anti-inflammatory Activity of β-Carotene, Lycopene and Tri-n-butylborane, a Scavenger of Reactive Oxygen Species. In Vivo. 2018 Mar-Apr; 32(2): 255-264.

[5]. Prooxidant effects of beta-carotene in cultured cells. Mol Aspects Med. 2003 Dec;24(6):353-62.

Therapeutic Uses
Antioxidant: Oral beta-carotene for the treatment of polymorphic light eruption; 32% (6/19) of patients received beta-carotene treatment achieved complete remission. Pharmaceutical Use (Veterinary): A vitamin A precursor in all species except cats. The long-term effects of oral beta-carotene (a carotenoid partially metabolized to retinol) on plasma lipid concentrations have not been adequately studied; therefore, this study included 61 participants in a skin cancer prevention study for 12 months. Patients were randomly assigned to receive either a placebo (n = 30) or 50 mg of beta-carotene daily (n = 31). Fasting blood samples were collected at the start of the study and one year later to measure triglyceride, total cholesterol, high-density lipoprotein cholesterol, retinol, and beta-carotene levels. Retinol concentrations changed very little in both groups; the placebo group saw a mean increase in β-carotene concentration of 12.1 ± 47 nmol/L, while the active treatment group saw a mean increase of 4279 ± 657 nmol/L. Similar slight increases in triglyceride and total cholesterol concentrations were observed in both groups, while high-density lipoprotein cholesterol concentrations showed a slight decrease. Daily oral administration of 50 mg of β-carotene did not affect plasma lipid concentrations. For more complete data on the therapeutic uses of β-carotene (out of 10), please visit the HSDB record page. Drug Warnings: β-carotene is ineffective in healthy individuals and should not be used for sun protection… Patients with impaired renal or hepatic function should use it with caution, as its safety has not been established. β-carotene is well tolerated. Carotene dermatitis is usually the only adverse reaction. Patients should be informed in advance that carotene dermatitis will appear 2–6 weeks after treatment, typically initially presenting as yellowing of the palms or soles, with milder yellowing of the face. Some patients may experience loose stools during beta-carotene treatment, but this is rare and usually does not require discontinuation of treatment. Reports of ecchymosis and joint pain are rare. Patients with impaired renal or hepatic function should use beta-carotene with caution, as its safety in these patients has not been established. Although abnormally high blood vitamin A levels are not observed during beta-carotene treatment, patients receiving beta-carotene should be advised against additional vitamin A supplementation, as beta-carotene itself meets normal vitamin A requirements. Patients should be reminded that consuming large amounts of green or yellow vegetables and their juices or extracts cannot replace crystalline beta-carotene, as excessive consumption of these vegetables may lead to adverse reactions such as leukopenia or menstrual disorders. Patients should be informed that the protective effect of beta-carotene is not entirely effective; patients may still experience significant burning sensations and edema after sufficient sun exposure. Each patient must determine their own exposure time limits. There are currently no adequate and well-controlled human studies. During pregnancy, beta-carotene should only be used if the potential benefits outweigh the potential risks to the fetus. The effects of beta-carotene on human fertility are not yet clear. For more drug warnings (full version) data on beta-carotene (11 in total), please visit the HSDB record page. Pharmacodynamics: Oral administration of beta-carotene can increase serum beta-carotene concentration by 60%, but does not alter concentrations in the heart, liver, or kidneys. In vitro hepatocyte studies have shown that beta-carotene can reduce oxidative stress, enhance antioxidant activity, and reduce apoptosis. In addition to its antioxidant activity, beta-carotene has other effects. It is believed to have detoxifying properties, help enhance resistance to inflammation and infection, improve immune responses, and enhance RNA production.

C40H56

536.8727

536.438

C, 89.49; H, 10.51

7235-40-7

5280489

Brown to red solid powder

0.9±0.1 g/cm3

654.7±22.0 °C at 760 mmHg

178-179ºC

346.0±17.2 °C

0.0±0.9 mmHg at 25°C

1.566

15.51

0

0

10

40

1120

0

C1(C([H])([H])[H])(C([H])([H])[H])C(/C(/[H])=C(\[H])/C(=C(\[H])/C(/[H])=C(\[H])/C(=C(\[H])/C(/[H])=C(\[H])/C(/[H])=C(\C([H])([H])[H])/C(/[H])=C(\[H])/C(/[H])=C(\C([H])([H])[H])/C(/[H])=C(\[H])/C2=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C2(C([H])([H])[H])C([H])([H])[H])/C([H])([H])[H])/C([H])([H])[H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C1([H])[H]

OENHQHLEOONYIE-JLTXGRSLSA-N

InChI=1S/C40H56/c1-31(19-13-21-33(3)25-27-37-35(5)23-15-29-39(37,7)8)17-11-12-18-32(2)20-14-22-34(4)26-28-38-36(6)24-16-30-40(38,9)10/h11-14,17-22,25-28H,15-16,23-24,29-30H2,1-10H3/b12-11+,19-13+,20-14+,27-25+,28-26+,31-17+,32-18+,33-21+,34-22+

1,3,3-trimethyl-2-[(1E,3E,5E,7E,9E,11E,13E,15E,17E)-3,7,12,16-tetramethyl-18-(2,6,6-trimethylcyclohexen-1-yl)octadeca-1,3,5,7,9,11,13,15,17-nonaenyl]cyclohexene

Beta carotene

2934.99.03.00

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

THF : 12.5 mg/mL (~23.28 mM)
DMSO : ~1 mg/mL (~1.86 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)