| In vitro: |
| 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. |
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