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
After administration of beta-carotene, some of the administered dose is absorbed into the circulatory system unchanged and stored in the fat tissue. The coadministration of beta-carotene and a high-fat content diet is correlated to a better absorption of beta-carotene. The absorption is also dependent on the isomeric form of the molecule where the cis conformation seems to present a higher bioavailability. The absorption of beta-carotene is thought to be performed in 6-7 hours. The reported AUC of beta-carotene when administered orally from 0 to 440 hours after initial administration was reported to be 26.3 mcg.h/L. The maximal concentration of beta-carotene is attained in a dual pharmacokinetic profile after 6 hours and again after 32 hours with a concentration of 0.58 micromol/L.
The unabsorbed carotene is excreted in feces. It is also excreted in feces and urine as metabolites. The consumption of dietary fiber can increase the fecal excretion of fats and other fat-soluble compounds such as beta-carotene.
No pharmacokinetic studies have been performed regarding the volume of distribution of beta-carotene.
The clearance rate of beta-carotene administered orally is 0.68 nmol/L each hour.
Carotenoids are absorbed and transported via lymphatics to the liver. They circulate in association with lipoproteins, and are found in liver, adrenal, testes, and adipose tissue, and can be converted to vitamin A in numerous tissues, including the liver. Some beta carotene is absorbed as such and circulates in association with lipoproteins; it apparently partitions into body lipids and can be converted to vitamin A in numerous tissues, including the liver.
Absorption of beta-carotene depends on the presence of dietary fat and bile in the intestinal tract.
Unchanged beta-carotene is found in various tissues, primarily fat tissues, adrenal glands, and ovaries. Small concentrations are found in the liver.
Only about one-third of beta-carotene or other carotenoids is absorbed by human beings. The absorption of carotenoids takes place in a relatively nonspecific fashion and depends upon the presence of bile and absorbable fat in the intestinal tract; it is greatly decreased by steatorrhea, chronic diarrhea, and very-low-fat diets.
For more Absorption, Distribution and Excretion (Complete) data for BETA-CAROTENE (9 total), please visit the HSDB record page.

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Metabolism / Metabolites
Beta-carotene is broken down in the mucosa of the small intestine and liver by beta-carotene dioxygenase to retinal which is a form of vitamin A. The function of this enzyme is vital as it decides if the beta-carotene is transformed to vitamin A or if it circulates in the plasma as beta-carotene. Less than a quarter of the ingested beta-carotene from root vegetables and about half of the beta-carotene from leafy green vegetables are converted to vitamin A.
A portion of the beta-carotene is converted to retinol in the wall of the small intestine, principally by its initial cleavage at the 15,15' double bond to form two molecules of retinal. Some of the retinal is further oxidized to retinoic acid; only one-half is reduced to retinol, which is then esterified and transported in the lymph. ...
Approximately 20 to 60% of beta-carotene is metabolized to retinaldehyde and then converted to retinol, primarily in the intestinal wall. A small amount of beta-carotene is converted to vitamin A in the liver. The proportion of beta-carotene converted to vitamin A diminishes inversely to the intake of beta-carotene, as long as the dosages are higher than one to two times the daily requirements. High doses of beta-carotene do not lead to abnormally high serum concentrations of vitamin A.
Beta carotene may be converted to 2 molecules of retinal by cleavage at the 15-15' double bond in the center of the molecule. Most of the retinal is reduced to retinol which is then conjugated with glucuronic acid and excreted in urine and feces. Some retinal may be further oxidized to retinoic acid which can be decarboxylated and further metabolized, secreted into bile, and excreted in feces as the glucuronide.
Two pathways have been suggested for the conversion of carotenoids to vitamin A in mammals, central cleavage and excentric cleavage. An enzyme, beta-carotenoid-15,15'-dioxygenase, has been partly purified from the intestines of several species and has been identified in several other organs and species. The enzyme, which converts beta-carotene into two molecules of retinal in good yield, requires molecular oxygen and is inhibited by sulfhydryl binding reagents and iron binding reagents. Most provitamin A carotenoids, including the beta-apo-carotenals, are cleaved to retinal by this enzyme. Its maximal activity in the rabbit is approximately 200 times that required to meet nutritional needs but is less than 50% of that expected to produce signs of vitamin A toxicity. Excentric cleavage unquestionably occurs in plants and some microorganisms and might occur in mammals. Thus far, however, carotenoid dioxygenase with excentric bond specificity has been identified in mammals, the yield of beta-apo-carotenals from beta-carotene in vivo and in vitro is very low, and beta-apo-carotenals are formed nonbiologically from beta-carotene.
The carotenes are not converted to retinol very rapidly, so that overdoses of the carotenes do not cause vitamin A toxicity. /Carotenes/

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Biological Half-Life
The apparent half-life of beta-carotene is of 6-11 days after initial administration.

Interactions
Cigarette smoking is associated with decreased plasma levels of ascorbate and beta-carotene, which indicates that the smoking related chronic inflammatory response leads to an imbalance of oxidant/antioxidant homeostasis and possible predisposition to oxidant inflicted tissue damage and disease.
Weanling male Sprague-Dawley rats were pair-fed beta-carotene (56.5 mg/L of diet) for 8 weeks, with and without ethanol. As expected, ethanol increased CYP2E1 (measured by Western blots) from 67 + or - 8 to 317 + or - 27 densitometric units (p < 0.001). Furthermore, beta-carotene potentiated the ethanol induction to 442 + or - 38 densitometric units (p < 0.01) with a significant interaction (p = 0.012). The rise was confirmed by a corresponding increase in the hydroxylation of p-nitrophenol, a specific substrate for CYP2E1, and by the inhibition with diethyl dithiocarbamate (50 microM). Beta-carotene alone also significantly induced CYP4A1 protein (328 + or - 49 vs. 158 + or - 17 densitometric units, p < 0.05). The corresponding CYP4A1 mRNA (measured by Northern blots) was also increased (p < 0.05) and there was a significant interaction of the two treatments (p = 0.015). The combination of ethanol and beta-carotene had no significant effect on either total cytochrome P-450 or CYP1A1/2, CYP2B, CYP3A, and CYP4A2/3 contents. Beta-carotene potentiates the CYP2E1 induction by ethanol in rat liver and also increases CYP4A1, which may, at least in part, explain the associated hepatotoxicity.
AFLATOXIN B1 (4 MG/KG/DAY, ORALLY) ADMIN TO RATS FOR 26 DAYS INHIBITED THE FORMATION OF VITAMIN A FROM BETA-CAROTENE IN THE INTESTINAL MUCOSA.
SULFITE-MEDIATED BETA-CAROTENE DESTRUCTION WAS INVESTIGATED; IT WAS INHIBITED BY ALPHA-TOCOPHEROL, 1,2-DIHYDROXYBENZENE-3,5-DISULFONIC ACID & BUTYLATED HYDROXYTOLUENE
For more Interactions (Complete) data for BETA-CAROTENE (25 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
Antioxidants
THERAPY WITH ORAL BETA-CAROTENE IN PATIENT WITH POLYMORPHOUS LIGHT ERUPTION; COMPLETE REMISSION OCCURRED IN 32% (6/19) TREATED WITH BETA-CAROTENE.
MEDICATION (VET): VITAMIN A PRECURSOR FOR ALL SPECIES EXCEPT CATS.
The effects of chronic oral administration of beta-carotene, a carotenoid partially metabolized to retinol, on plasma lipid concentrations have not been well studied; therefore, 61 subjects were studied over 12 mo while they were enrolled in a skin cancer prevention study in which patients were randomly assigned to receive either placebo (n = 30) or 50 mg beta-carotene/day orally (n = 31). At study entry and 1 yr later, fasting blood samples were obtained for measurement of triglycerides, total cholesterol, high density lipoprotein cholesterol, retinol, and beta-carotene. Retinol concentrations changed minimally in both groups; beta-carotene concentration increased an average of 12.1 + or - 47 nmol/L in the placebo group and 4279 + or - 657 nmol/l in the active treatment group. Both groups experienced similar small increases in triglyceride and total cholesterol concentrations and small decreases in high density lipoprotein cholesterol. Daily oral administration of 50 mg beta-carotene/day did not affect plasma lipid concentrations.
For more Therapeutic Uses (Complete) data for BETA-CAROTENE (10 total), please visit the HSDB record page.

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Drug Warnings
NOT EFFECTIVE AS SUNSCREEN IN NORMAL INDIVIDUALS & SHOULD NOT BE USED FOR THAT PURPOSE ... USED WITH CAUTION IN PT WITH IMPAIRED RENAL OR HEPATIC FUNCTION BECAUSE SAFE USE ... HAS NOT BEEN ESTABLISHED.
Beta carotene is well tolerated. Carotenodermia is usually the only adverse effect. Patients should be forewarned that carotenodermia will develop after 2-6 weeks of therapy, usually first noticed as yellowness of the palms of the hands or soles of the feet and to a lesser extent of the face. Some patients may experience loose stools during beta carotene therapy, but this is sporadic and may not require discontinuance of therapy. Ecchymoses and arthralgia have been reported rarely
Beta carotene should be used with caution in patients with impaired renal or hepatic function because safe use of the drug in the presence of these conditions has not been established. Although abnormally high blood concentrations of vitamin A do not occur during beta carotene therapy, patients receiving beta carotene should be advised against taking supplementary vitamin A because beta carotene will fulfill normal vitamin A requirements. Patients should be cautioned that large quantities of green or yellow vegetables or their juices or extracts are not suitable substitutes for crystalline beta carotene because consumption of excessive quantities of these vegetables may cause adverse effects such as leukopenia or menstrual disorders. Patients should be warned that the protective effect of beta carotene is not total and that they may still develop considerable burning and edema after sufficient exposure to sunlight. Each patient must establish his own time limit of exposure.
There are no adequate and controlled studies to date in humans. Beta carotene should be used during pregnancy only when the potential benefits justify the possible risks to the fetus. The effect of beta carotene on fertility in humans is not known.
For more Drug Warnings (Complete) data for BETA-CAROTENE (11 total), please visit the HSDB record page.

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Pharmacodynamics
Oral administration of beta-carotene increases the serum concentration of beta-carotene by 60% but it does not change the concentration found in the heart, liver or kidneys. In vitro studies in hepatocytes have shown that beta-carotene ameliorates oxidative stress, enhances antioxidant activity and decreases apoptosis. Other than the antioxidant activities, some other actions have been correlated to beta-carotene. It is thought to have detoxifying properties, as well as to help increase resistance to inflammation and infection and increase immune response 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.)