Dr. Weeks’ Comment: If you have cancer, learn about the only cancer cells which can metastasize, the same ones which are resistant to chemo and radiation. These are called your cancer stem cells. Ask your oncologist what her or his proposed therapy will do to your cancer stem cells? Dr. Max Wicha, Distinguished Professor of Oncology at U Michigan warns: Chemotherapy and radiation can make your cancer worse.
Has your oncologist heard about the nutritional supplement called Chrysin?
It is commonly found in the plant Passiflora coerulea, is structurally defined as 5,7-dihydroxyflavone. Chrysin has demonstrated an ability to maximize testosterone by inhibiting aromatase activity. Aromatase is the enzyme responsible for the conversion of androstenedione and testosterone into esterone and esterdiol respectively.
Chrysin Reverse the Drug Resistance by Targeting Breast Cancer Stem Cell Related Subpopulation
Part one : The study of construction and drug reversion in MCF-7/MX cell lines
Objective: To study Chrysin reverse the drug resistance in MCF-7/MX cell lines.
Methods: To establish the MCF-7/MX cell line by stepwise selection in mitoxantrone . Study the characteristics of MCF-7 cell lines and characterized the expression of BCRP by using Western blot analysis. Investigate Effects of Chrysin on Mitoxantrone Cytotoxicity in MCF-7 cell line by using MTT way.
Results: The MCF-7/MX cell line can be constructed by stepwise selection in mitoxantrone. MCF-7 cells had no detectable BCRP expression , however, BCRP is clearly overexpressed in mitoxantrone-selected MCF-7/MX cells and gradually increase when mitoxantrone increase from 8nM to 100nM. After being induced by mitoxantrone,cell multiplication time of MCF-7/MX cells is 37.87hour and the multidrug resistance index increased to 38 fold but chrysin can reverse drug resistance.In the MCF-7/MX cells, chrysin dramatically lowered the IC50 value of mitoxantrone from 19.954±0.190μM to 1.851±0.02μM、0.62±0.217μM (P < 0.05),similar to the IC50 value in the MCF-7 cells . In the presence of chrysin (2.5μM,5μM), the IC50 value of mitoxantrone in MCF-7 cells was not significantly changed .
Conclusions: 1、The MCF-7/MX cell line can be constructed by stepwise selection in mitoxantrone .
2、After being induced by mitoxantrone, MCF-7/MX cells is highly drug-resistant .
3、Chrysin can reverse drug resistance of MCF-7/MX cells by targeting BCRP.
Part Two : Chrysin influences breast cancer stem cell Subgroup in MCF-7/MX cell lines
Objective: To Investigate the influence of chrysin on CD44~+CD24~- cell in MCF-7/MX cell lines
Methods: We used FACSC and Cell immunofluorescence to analyse the percentage of CD44~+ CD24~- cells in MCF-7 and MCF-7/MX cell lines.Results: Nearly 95% cells of MCF-7/MX and MCF-7 cell is CD44~+CD24~+. The percentage of the CD44~+CD24~-cells in MCF-7/MX cells was was not significantly changed by only Chrysin treatment relative to the CD44~+CD24~-cells in untreated cells (P > 0.05).The percentage of the CD44~+CD24~-cells in MCF-7/MX cells was decreased by Chrysin and Mitoxantrone treatment relative to the CD44~+CD24~-cells found at 3.2% in untreated cells. In MCF-7/MX cells treated by Chrysin and Mitoxantrone, the CD44~+CD24~-cells population was 2.684±0.226%,1.907±0.179 %,1.414±0.112 % and 1.448±0.057% at 10-2μM、10-1μM、100μM、101μM Chrysin , respectively(P < 0.05).
The same results could be Investigate by using Cell immunofluorescence.Conclusions: MCF-7/MXcells are Sensitive to mitoxantrone fowllowing the chrysin treatment.
The percentage of the CD44~+CD24~-cells in MCF-7/MX cells was not significantly changed by only Chrysin treatment,so the chrysin can only become chemotherapy sensitizer.