Indole-3-carbinol

Indole-3-carbinol suppresses NF-κB activity and also is an Aryl hydrocarbon receptor (AhR) agonist.

Signaling Pathways >> Immunology/Inflammation >> Aryl Hydrocarbon Receptor

Natural Products >> Alkaloid

Research Areas >> Cancer

NF-κB

AhR

It is found that Indole-3-carbinol (I3C) inhibits the proliferation of THP-1 cells in a dose- and time dependent manner with minimal toxicity over normal monocytes. The AhR target genes (CYP1A1, IL1β) are overexpressed upon Indole-3-carbinol treatment (p<0.05 to p<0.001). The antiproliferative effects of Indole-3-carbinol are in association with programing cell death. Indole-3-carbinol downregulates BCL2 and upregulates FasR in THP-1 cells (p<0.05 to p<0.001). G1 cell cycle arrest is also observed using flow cytometry. G1-acting cell cycle genes (P21, P27 and P53) are overexpressed (p<0.05 to p<0.001), while CDK2 is downregulated upon Indole-3-carbinol treatment (p<0.01 to p<0.001)[1].Indole-3-carbinol suppresses NF-κB activity and stimulates the p53 pathway in pre-B acute lymphoblastic leukemia cells[2].

THP-1 cells are cultured in RPMI 1640 supplemented with 10% FBS, 100 U/mL penicillin, 100 mg/mL streptomycin and 2 mM Glutamax in a fully humidified atmosphere with 5% CO2. Cells (2-5×105 mL-1) are seeded in six well plates followed by resuspension in complete growth media. THP-1 monocyte cells are then treated with 10 ng/mL phorbol 12-myristate 13-acetate as a tumor promoter to induce stable differentiation into attaching macrophage-like cells and overexpression of AhR. The cells are then treated with varying concentrations of Indole-3-carbinol (1, 10 and 100 μM, and 1 mM). THP-1 cells and enriching normal monocytes are seeded at 5×104 cells/well in 24-well plate with different concentrations of Indole-3-carbinol and observed for 24 and 48 h followed by MTT assay. The cells are incubated in triplicates in a final volume of 200 mL of Phenol Red free RPMI 1640 for 20 h . An aliquot of 20 mL of MTT solution (5 mg/mL) is added to each well and incubated for 4 h. Formazan crystals are formed. An amount of 300 mL DMSO is then added to each well as a cell lysis solution. Percentage of cell viability is assessed by spectrophotometry at 570 nm[1].

[1]. Mohammadi S, et al. Indole-3-carbinol induces G1 cell cycle arrest and apoptosis through aryl hydrocarbon receptor in THP-1 monocytic cell line.J Recept Signal Transduct Res. 2017 Oct;37(5):506-514.

[2]. Safa M, et al. Indole-3-carbinol suppresses NF-κB activity and stimulates the p53 pathway in pre-B acute lymphoblastic leukemia cells. Tumour Biol. 2015 May;36(5):3919-30.

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DATA ITEMS CITED :

5

MOLECULAR FORMULA :

C9-H9-N-O

MOLECULAR WEIGHT :

147.19

WISWESSER LINE NOTATION :

T56 BMJ D1Q

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

500 mg/kg

TOXIC EFFECTS :

Behavioral - coma

REFERENCE :

FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 18,159,1980 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

9100 mg/kg/13W-I

TOXIC EFFECTS :

Liver - jaundice (or hyperbilirubinemia) hepatocellular Liver - changes in liver weight

REFERENCE :

TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981- Volume(issue)/page/year: 15,292,1995

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

5600 mg/kg/13W-I

TOXIC EFFECTS :

Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981- Volume(issue)/page/year: 15,292,1995 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1 mg/kg

SEX/DURATION :

female 15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - delayed effects

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 141,68,1996

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

400 mg/kg

SEX/DURATION :

female 8-9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :

FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 18,159,1980