3',4'-Dimethoxyflavone

Toxicological Sciences, 2001, 58(2):235-242.

3′,4′-Dimethoxyflavone as an Aryl Hydrocarbon Receptor Antagonist in Human Breast Cancer Cells.[Reference: WebLink]

METHODS AND RESULTS:
Treatment of MCF-7 and T47D human breast cancer cells with 3',4'-Dimethoxyflavone (3′,4′-DMF) alone did not induce CYP1A1-dependent ethoxyresorufin O-deethylase (EROD) activity or reporter gene activity in cells transfected with an aryl hydrocarbon (Ah)-responsive construct (pRNH11c). In contrast, 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced up to a 50- to 80-fold increase in EROD and reporter gene activity in MCF-7 and T47D cells. In cells cotreated with 1 nM TCDD plus 0.1–10 μM 3′,4′-DMF, there was a concentration-dependent decrease in the TCDD-induced responses, with 100% inhibition observed at the 10 μM concentration. Gel mobility shift assays using rat liver cytosol and breast cancer cell nuclear extracts showed that 3′,4′-DMF alone did not transform the AhR to its nuclear binding form, but inhibited TCDD-induced AhR transformation in rat liver cytosol and blocked TCDD-induced formation of the nuclear AhR complex in MCF-7 and T47D cells.
CONCLUSIONS:
TCDD also inhibited estrogen-induced transactivation in MCF-7 cells, and this response was also blocked by 3′,4′-DMF, confirming the AhR antagonist activity of this compound in breast cancer cells.

Stem Cell Research & Therapy, 2013, 4(3):1-8.

3′,4′-Dimethoxyflavone and valproic acid promotes the proliferation of human hematopoietic stem cells.[Reference: WebLink]

Human hematopoietic stem cells (HSCs) have been clinically used for transplantation and gene and cellular therapy for more than 4 decades. However, this use is limited because of the challenges in the ex vivo culturing of HSCs. The major hurdle is to amplify these cells without losing their self-renewing property.
METHODS AND RESULTS:
In our study, we tested 3',4'-Dimethoxyflavone (3′4′-DMF) and valproic acid (VPA) on the ex vivo expansion of HSCs under both normoxic (20% O2) and hypoxic (1% O2) conditions. 3′4′-DMF is a widely used anticancer drug that acts as a competitive antagonist of the aryl hydrocarbon receptor. VPA is a potent inhibitor of histone deacetylase and is used in the treatment of neurologic disorders. Culturing HSCs (from mobilized peripheral blood) under normoxia, with 3′4′-DMF and VPA, highly preserved the CD34 positivity (3′4′-DMF, 22.1%, VPA, 20.3%) after 1 week and strongly enhanced the CD34+ cells (3′4′-DMF, 27.8 fold; VPA, 34.1 fold) compared with the control cultures (11.6% and 14.4 fold). Addition of 3′4′-DMF and VPA also resulted in more primary colonies and replating efficiency compared with control cultures. Although no significant effect was observed on the enhancement of CD34+ cells under hypoxia, the number of primary colonies was significantly higher than the control cultures.
CONCLUSIONS:
Based on these findings, this study presents, for the first time, in vitro evidence for a new and relevant effect of 3′4′-DMF on human HSCs. In addition, the results suggest a potential clinical use of 3′4′-DMF and VPA in HSC therapy.

Korean Journal of Nutrition, 2009, 42(3).

Composition of Flavonoids and Antioxidative Activity from Juice of Jeju Native Citrus Fruits during Maturation.[Reference: WebLink]

This study aims to evaluate the changes of flavonoid contents and antioxidants activity of Jeju native citrus fruits juice according to the harvest date.
METHODS AND RESULTS:
Flavonoids such as quercatagetin, narirutin, hesperidin and neohesperidin were contained most plentifully in the juice of Jigak (Citrus aur- antium) by 573.73 mg/100 mL, Sadoogam (C. pseudogulgul) by 393.99 mg/100 mL, Soyooja by 29.63 mg/100 mL and Jigak (C. aurantium) by 201.23 mg/100 mL in the late August, respectively. The highest contents of nob-iletin, sinensetin and tangeretin among polymethoxyflavones were found in the juice of Hongkyool (C. tachibana) by 7.39 mg/100 mL, 2.24 mg/100 mL, 0.63 mg/100 mL in the late August, respectively. 3,5,6,7,8,3',4'-Heptamet-hoxyflavone recorded the highest amount in Punkyool (C. tangerina) by 0.27 mg/100 mL in the late August, but the other polymethoxyflavones including 3',4',7,8-tetramethoxyflavone, 3',4'-Dimethoxyflavone, 4'-methoxyflavone, 5,6,7,3',4',5'-hexamethoxyflavone, scutellarein tetramethylether were observed only trace amount in all the citrus fruits. Flavonoid contents in the citrus fruit juices were the highest during early maturation and decreased rapidly while ripening. Total polyphenol contents were the highest in the late August and decreased with ripening. However from the late December, the contents were increased again. Antioxidant activities of the fruits were evaluated as electron donating ability and were the lowest in the late September and increased with the fruit ripening.
CONCLUSIONS:
These results suggest that quercetagetin among all the flavonoids was most plentiful in Jigak and Dangyooja (C. grandis), so that the fruits could be used for industrial material of flavonoids and antioxidant agents.