Obacunone (AI3-37934)

Catalog No.S3784 Batch:S378401

Technical Data

Formula	C₂₆H₃₀O₇
Molecular Weight	454.51	CAS No.	751-03-1
Solubility (25°C)*	In vitro	DMSO	90 mg/mL (198.01 mM)


* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

Obacunone (AI3-37934, CCRIS 8657), a natural compound present in citrus fruits, has been demonstrated for various biological activities including anti-cancer and anti-inflammatory properties. It significantly inhibits aromatase activity in an in vitro enzyme assay with an IC50 value of 28.04 μM; also a novel activator of Nrf2.

Targets

Nrf2 ^[2]	Aromatase ^[1] (Cell-free assay)
	28.4 μM

In vitro

Obacunone is strongly inhibited MCF-7 cell proliferation without affecting non-malignant breast cells. Treatment with obacunone increases apoptosis by upregulating expression of the pro-apoptotic protein Bax and down-regulating the anti-apoptotic protein Bcl2, as well as inducing G1 cell cycle arrest. In addition, obacunone significantly inhibits aromatase activity in an in vitro enzyme assay. Exposure of MCF-7 breast cancer cells to obacunone down-regulates expression of inflammatory molecules including nuclear factor-kappa B (NF-kB) and cyclooxygenase-2 (COX-2). Obacunone inhibits COX-2 and NF-kB by activation of the p38 mitogen-activated protein kinase (MAPK). Obacunone is reported as a glutathione S-transferase (GST) enzyme inducer as well as a neuroprotective agent acting by induction of heme oxygenase-1 via the p38 MAPK pathway^[1]. Obacunone is a novel activator of Nrf2 by decreasing Nrf2 ubiquitination and increasing its stability. It can effectively protect cells from oxidative stress by activating the Nrf2 pathway. Obacunone could induce the expression of the ARE-dependent luciferase gene in a dose-dependent manner^[2].

In vivo

The systemic administration of obacunone strongly inhibits bleomycin-induced lung fibrosis in mice. Obacunone can inhibit cancer proliferation and has some therapeutic effects on cardiovascular diseases^[2]. In vitro and animal studies suggests that obacunone and a few other limonoids may have potential anticarcinogenic activity against certain types of cancers. A 500-mg/kg (of body weight) dose of obacunone per day is well tolerated and does not have adverse effects in rats, indicating a low toxicity^[3].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Human breast cancer (MCF-7) and non-malignant immortalized breast epithelial (MCF-12F) cell lines Concentrations 12.5, 25, 50,100 and 200 μM Incubation Time 24, 48, and 72 h Method The MCF-7 cells are cultured in DMEM medium containing 10% (v/v) fetal bovine serum, 200 U/mL penicillin G, and 200 mg/mL streptomycin. The MCF-12F cells are cultured in a 1:1 mixture of DMEM and Ham's F12 medium with 20 ng/mL of epidermal growth factor (EGF),100 ng/mL cholera toxin, 0.01 mg/mL insulin, 500 ng/mL hydrocortisone, and 5% (v/v) chelextreated horse serum, and then the cells are incubated at 37℃ with 5% CO2. To evaluate the anti-proliferate effects of obacunone, viability of the MCF-7 and MCF-12F cells are measured using the tetrazolium MTT reduction assay. The MCF-7 or MCF-12F cells (1×10⁴/well) are seeded into a 96-well plate and allowed to adhere overnight. Cells are treated with different concentrations (12.5, 25, 50,100 and 200 μM) of either obacunone or OG and incubated for 24, 48, and 72 h. Tamoxifen, a well-known anti-estrogen drug used for breast cancer therapy, is used as a positive control. After the various time points, 10 ml of the MTT (5 mg/mL) reagent are added to each well and incubated for 2h at 37℃. After 2h incubation, the medium is removed and 200 ml of DMSO is added to dissolve the purple formazan. The absorbance is measured by an ELISA microplate reader at 570 nm.
Animal Study:^{^[2]}	Animal Models Eight-week-old B6 mice Dosages 10 mg/kg Administration i.p.

Cell Assay:^{^[1]}

Cell lines
Human breast cancer (MCF-7) and non-malignant immortalized breast epithelial (MCF-12F) cell lines
Concentrations
12.5, 25, 50,100 and 200 μM
Incubation Time
24, 48, and 72 h
Method
The MCF-7 cells are cultured in DMEM medium containing 10% (v/v) fetal bovine serum, 200 U/mL penicillin G, and 200 mg/mL streptomycin. The MCF-12F cells are cultured in a 1:1 mixture of DMEM and Ham's F12 medium with 20 ng/mL of epidermal growth factor (EGF),100 ng/mL cholera toxin, 0.01 mg/mL insulin, 500 ng/mL hydrocortisone, and 5% (v/v) chelextreated horse serum, and then the cells are incubated at 37℃ with 5% CO2. To evaluate the anti-proliferate effects of obacunone, viability of the MCF-7 and MCF-12F cells are measured using the tetrazolium MTT reduction assay. The MCF-7 or MCF-12F cells (1×10⁴/well) are seeded into a 96-well plate and allowed to adhere overnight. Cells are treated with different concentrations (12.5, 25, 50,100 and 200 μM) of either obacunone or OG and incubated for 24, 48, and 72 h. Tamoxifen, a well-known anti-estrogen drug used for breast cancer therapy, is used as a positive control. After the various time points, 10 ml of the MTT (5 mg/mL) reagent are added to each well and incubated for 2h at 37℃. After 2h incubation, the medium is removed and 200 ml of DMSO is added to dissolve the purple formazan. The absorbance is measured by an ELISA microplate reader at 570 nm.

Animal Study:^{^[2]}

Animal Models
Eight-week-old B6 mice
Dosages
10 mg/kg
Administration
i.p.

References

Selleck's Obacunone (AI3-37934) has been cited by 2 publications

Obacunone Photoprotective Effects against Solar-Simulated Radiation-Induced Molecular Modifications in Primary Keratinocytes and Full-Thickness Human Skin [ Int J Mol Sci, 2023, 24(14)11484]	PubMed: 37511243
Obacunone alleviates ferroptosis during lipopolysaccharide-induced acute lung injury by upregulating Nrf2-dependent antioxidant responses [ Cell Mol Biol Lett, 2022, 27(1):29]	PubMed: 35305560

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SHIPPING AND STORAGE
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