3,3'-Diindolylmethane

Names

[ CAS No. ]:
1968-05-4

[ Name ]:
3,3'-Diindolylmethane

[Synonym ]:
HB 236
1H-Indole, 2-(1H-indol-3-ylmethyl)-
3-(1H-indol-3-ylmethyl)-1H-indole
ARUNDINE
di(1H-indol-3-yl)methane
DI-3-INDOLYLMETHANE
DIM
3-DIINDOLYL METHANE
3,3'-Diindolylmethane
1H-Indole, 3,3'-methylenebis-
2-(1H-Indol-3-ylmethyl)-1H-indole
3,3'-Methylenediindole
3,3'-Methylenebisindole；DIM
DI INDOLYL METHANE
di-(1H-3-indolyl)methane
Indole dimer
3,3'-methylene-bis(1H-indole)
3,3-Methylenediindole
Indolyl-CH2-Indolyl
MFCD00195766
3,3'-Methylenebis(1H-indole)
3,3'-Diindolymetane
Diindole methane

Biological Activity

[Description]:

3,3'-Diindolylmethane is a strong, pure androgen receptor (AR) antagonist.

[Related Catalog]:

Signaling Pathways >> Others >> Androgen Receptor

Research Areas >> Cancer

Natural Products >> Others

[Target]

Androgen receptor[1]

[In Vitro]

3,3'-Diindolylmethane (DIM) is a strong antagonist of androgen receptor (AR) function but exhibits less than obvious structural similarity to the endogenous AR ligand, dihydrotestosterone (DHT). 3,3'-Diindolylmethane is a major digestive product of indole-3-carbinol, a potential anticancer component of cruciferous vegetables. 3,3'-Diindolylmethane exhibits potent antiproliferative and antiandrogenic properties in androgen-dependent human prostate cancer cells. 3,3'-Diindolylmethane suppresses cell proliferation of LNCaP cells and inhibits DHT stimulation of DNA synthesis. Moreover, 3,3'-Diindolylmethane inhibits endogenous PSA transcription and reduced intracellular and secreted PSA protein levels induced by DHT in LNCaP cells. Also, 3,3'-Diindolylmethane inhibits, in a concentration-dependent manner, the DHT-induced expression of a prostate-specific antigen promoter-regulated reporter gene construct in transiently transfected LNCaP cells. Co-treatment with 50 μM 3,3'-Diindolylmethane partially inhibits the translocation of AR induced by DHT treatment and showed distribution of the AR to be both cytoplasmic and nuclear. Furthermore, 3,3'-Diindolylmethane treatment prevents the formation of AR foci in the nucleus. 3,3'-Diindolylmethane alone produces a predominantly cytoplasmic distribution of fluorescence[1].

[In Vivo]

Mice are randomized into two groups and are treated daily s.c. with either vehicle or 3,3'-Diindolylmethane (10 mg/kg) for 30 days. Tumor volume and the weight of mice are recorded once every 3 days using calipers. 3,3'-Diindolylmethane (DIM) treatment resulted in a marked inhibition of SNU-484 xenograft tumor growth. Notably, the body weight of mice from both groups did not significantly differ from the vehicle control following 30 days of drug exposure, suggesting that 3,3'-Diindolylmethane has no severe toxicity to the mice. Taken together, these findings demonstrate that 3,3'-Diindolylmethane administration significantly inhibited SNU-484 xenograft growthin vivo mediated by the inactivation of YAP[2].

[Cell Assay]

The human prostate adenocarcinoma cell lines LNCaP-FGC and PC-3 are grown as adherent monolayers in 10% FBS-DMEM, supplemented with 4.0 g/L glucose and 3.7 g/L sodium bicarbonate in a humidified incubator at 37°C and 5% CO2, and passaged at ~80% confluency. Cultures used in subsequent experiments are at less than 40 passages. Cells grown in stripped conditions are in 5% DCC-FBS-DMEM base supplemented with 4 g/L glucose, 3.7 g/L sodium bicarbonate, and 0.293 g/L L-glutamine. Before the beginning of the treatments, cells are depleted of androgen for 4-7 days in medium composed of DMEM base without phenol red and with 4 g/L glucose and 3.7 g/L sodium bicarbonate. During the depletion period, medium is changed every 48 h. Treatments are administered by the addition of 1 μL of a 1,000-fold concentrated solution of 3,3'-Diindolylmethane in Me2SO/mL of medium. Once the treatment period started, medium is changed daily to counter possible loss of readily metabolized compounds[1].

[Animal admin]

Mice[2] Four-week-old female SPF/VAF immunodeficient mice are injected subcutaneously (s.c.) into the right flank with 0.1 mL Matrigel containing 3.5×106 human gastric cancer cells (SNU-484). The mice are randomized into 2 groups 1 week after tumor implantation: i) the untreated control group (n=5, DMSO in 50 μL PBS daily) and ii) the 3,3'-Diindolylmethane-treated group (n=5, 10 mg/kg in 50 μL PBS once daily). Gastric primary tumors are excised, and the final tumor volume is measured once every 3 days using a caliper and calculated as (width)2×length/2. The experiment is terminated on day 39. Half of the tumor tissue is prepared for western blotting and the other half is snap frozen in liquid nitrogen and stored at −80°C.

[References]

[1]. Le HT, et al. Plant-derived 3,3'-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem. 2003 Jun 6;278(23):21136-45.

[2]. Li XJ, et al. 3,3'-Diindolylmethane suppresses the growth of gastric cancer cells via activation of the Hippo signaling pathway. Oncol Rep. 2013 Nov;30(5):2419-26.

[Related Small Molecules]

ARN-509 | Dehydroepiandrosterone | Flutamide | ODM-201 | Danazol | AZD3514 | RAD140 | BMS-564929 | GLPG0492 | Cyproterone acetate | LGD-4033 | Lupeol | Andarine | MK-0773 | ORM-15341

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
504.8±30.0 °C at 760 mmHg

[ Melting Point ]:
167 °C

[ Molecular Formula ]:
C₁₇H₁₄N₂

[ Molecular Weight ]:
246.307

[ Flash Point ]:
232.5±15.8 °C

[ Exact Mass ]:
246.115692

[ PSA ]:
31.58000

[ LogP ]:
4.05

[ Vapour Pressure ]:
0.0±1.2 mmHg at 25°C

[ Index of Refraction ]:
1.765

[ Storage condition ]:
2-8°C

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335-H413

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
36/37/38

[ Safety Phrases ]:
22-24/25

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
NM0332000

[ HS Code ]:
2933990090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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