Quercetin And Its Metabolites In Human Breast Cancer MCF-7 Cells In Vitro Anti-tumor Effect

In this study we investigated the anticancer effects of Quercetin (Q), Quercetin-3’-sulfate sodium salt (Q3S), Quercetin-3’-glucuronide sodium salt (Q3G), Isorhamnetin (IS) and Isorhamnetin-3’-glucuronide sodium salt (I3G) in vitro. We selected the human breast MCF-7cancer cell lines which were in the exponential phase of growth as experimental model to detect the viabilities of MCF-7cancer cells by MTT assay. The study found that quercetin and its derivatives inhibited the proliferation of MCF-7cancer cells in a dose-dependent manner and the higher medicine concentration was, the lower survival rate of cancer cells were. When the MCF-7cancer cells were treated with Q, IS and Q3S at the dose of100μM for48h, the percentage of cell viability were33.1%,34.2%and36.2%. We evaluated the cytotoxicity of flavonoids on MCF-7cancer cells by LDH assay, Treated with Q, IS and Q3S at the concentration of100μM for48h, the LDH leakage of cancer cells were1389.7U/L,1359.4U/L and1327.1U/L respectively. The morphological changes of cancer cells were observed by Hoechst33258staining, When we treated the cancer cells with Q, IS and Q3S of100μM for48h, there were clear changes in cell morphology, such as condensed nuclei and apoptotic bodies. Assessment of apoptosis was performed by flow cytometry using annexin V-FITC and PI labeling, When MCF-7cells were exposured to100μM Q, IS and Q3S for48h, the percentage of cells in the early apoptosis were70.8%,68.9%å'Œ58.18%, respectively. The effect of flavonoids on cell cycle in MCF-7cancer cells was assessed by flow cytometry, When MCF-7cells were exposured to100μM Q, IS and Q3S for48h, there were50.35%,47.43%and42.04%cells accumulated in the S-phase, this suggested that drugs could induce S-phase growth arrest of the cancer cells. The change of cell reactive oxygen species were assayed by flow cytometry, When MCF-7cells were exposured to100μM Q, IS and Q3S for12h, the accumulation of H2O2were68.14%,55.83%and51.13%, and the accumulation of O2-were84.1%,77.6%and70.27%respectively.This study found that Q, IS and Q3S had much stronger growth-inhibitory potential in human breast cancer cell MCF-7, in comparison with structurally related substances Q3G and I3G. This study is important to the research and development of new flavonoids in future.