Quercetin

Quercetin is a natural flavonoid which activates or inhibits the activities of a number of proteins. Quercetin can activate SIRT1 and inhibit PI3K with IC50s of 2.4 μM, 3.0 μM, 5.4 μM for PI3K γ, PI3K δ and PI3K β, respecti

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Autophagy >> Mitophagy

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

Natural Products >> Flavonoids

Research Areas >> Cancer

PI3Kβ:5.4 μM (IC50)

PI3Kδ:2.4 μM (IC50)

PI3Kγ:3 μM (IC50)

Autophagy

Mitophagy

Quercetin is a type of plant-based chemical, or phytochemical, used as an ingredient in supplements, beverages or foods. In several studies, it may have anti-inflammatory and antioxidant properties, and it is being investigated for a wide range of potential health benefits. Quercetin is a PI3K inhibitor with IC50 of 2.4-5.4 μM. It strongly abrogates PI3K and Src kinases, mildly inhibits Akt1/2, and slightly affected PKC, p38 and ERK1/2[1]. Quercetin inhibits TNF-induced LDH% release, EC-dependent neutrophils adhesion to bovine pulmonary artery endothelial cells (BPAEC), and BPAEC DNA synthesis and proliferation[2].

Combination of Quercetin (75 mg/kg) and 2-Methoxyestradiol enhances inhibition of human prostate cancer LNCaP and PC-3 cells xenograft tumor growth[3].

Mice are inoculated subcutaneously with 5×105 PC-3 cells suspended in 100μL PBS and 2×108 LNCaP cells suspended in 100μL of matrigel and PBS mixture (1:1) on the right back. When xenograft tumors reach a volume of approximately 100 mm3, mice are randomLy assigned to four groups (n=8 each group) and treated intraperitoneally. Therapeutic schedule based on our in vitro results, preliminary experiments and many other researchers' studies is as follows: (1) Vehicle control group: vehicle of quercetin on day 1, vehicle of 2-ME on day 2, (2) Quercetin treated group: quercetin 75 mg/kg on day 1, vehicle of 2-ME on day 2, (3) 2-ME treated group: vehicle of quercetin on day 1, 2-ME 150 mg/kg on day 2, (4) Combination treatment group: quercetin 75 mg/kg on day 1, 2-ME 150 mg/kg on day 2. Two days is a treatment cycle and the whole treatment process lasted for 4 weeks. Tumor sizes are monitored every 2 days using caliper and tumor volume are calculated according to the formula: L×S2×0.5, in which L represents the longest diameter and S represents the shortest diameter of tumor. Mice are weighed as well. At the end of treatment procedure, on day 29, mice are anesthetized with chloral hydrate and sacrificed by cervical dislocation. Xenograft tumors are taken out quickly and weighed. One part of it is put into liquid nitrogen immediately for future biomarker analysis and the other part is fixed in 10% neutral buffered formalin for immunohistochemical analysis. Serum biochemical parameters such as ALT, AST, creatinine and urea nitrogen that reflected drug toxicity are also detected.

[1]. Navarro-Nú?ez L, et al. Effect of quercetin on platelet spreading on collagen and fibrinogen and on multiple platelet kinases. Fitoterapia. 2010 Mar;81(2):75-80.

[2]. Yu XB, et al. Inhibitory effects of protein kinase C inhibitors on tumor necrosis factor induced bovine pulmonary artery endothelial cell injuries. Yao Xue Xue Bao. 1996;31(3):176-81.

[3]. Yang F, et al. Combination of Quercetin and 2-Methoxyestradiol Enhances Inhibition of Human Prostate Cancer LNCaP and PC-3 Cells Xenograft Tumor Growth. PLoS One. 2015 May 26;10(5):e0128277.

3-Methyladenine | LY294002 | SB203580 | U0126-EtOH | Acadesine (AICAR) | Wortmannin | Brefeldin A | Alpelisib (BYL719) | 17-AAG | Resveratrol | BKM120 | Eganelisib(IPI-549) | Melatonine | Curcumin | Salinomycin

DATA ITEMS CITED :

60

MOLECULAR FORMULA :

C15-H10-O7

MOLECULAR WEIGHT :

302.25

WISWESSER LINE NOTATION :

T66 BO EVJ CR CQ DQ& DQ GQ IQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

161 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

159 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - muscle weakness Lungs, Thorax, or Respiration - respiratory depression

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

3 gm/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

97 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - muscle weakness Lungs, Thorax, or Respiration - respiratory depression

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

18 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

33610 mg/kg/58W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Gastrointestinal - tumors Kidney, Ureter, Bladder - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

966 gm/kg/23W-C

TOXIC EFFECTS :

Tumorigenic - equivocal tumorigenic agent by RTECS criteria Lungs, Thorax, or Respiration - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

38235 mg/kg/58W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Gastrointestinal - tumors Kidney, Ureter, Bladder - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

243 gm/kg/3Y-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

487 gm/kg/3Y-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Liver - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

20 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

16 mg/kg

SEX/DURATION :

male 5 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Sperm Morphology

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Micronucleus test

MUTATION DATA

TYPE OF TEST :

DNA inhibition

TEST SYSTEM :

Mammal - cattle Cells - not otherwise specified

DOSE/DURATION :

12 umol/L

REFERENCE :

EXPEAM Experientia. (Birkhaeuser Verlag, POB 133, CH-4010 Basel, Switzerland) V.1- 1945- Volume(issue)/page/year: 44,882,1988 *** REVIEWS *** IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 31,213,1983 IARC Cancer Review:Human No Adequate Data IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 31,213,1983 IARC Cancer Review:Group 3 IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,56,1987