Evaluation Of Flavonoids On Cell Proliferation In Cancer Cells And The Construction Of Drug Resistance Cell Line MDA-MB-453/BCRP

The flavonoids in most plants are polyphenolic compounds possessing a skeleton which can be presented as C₆ - C₃ - C₆ system. These compounds display a wide spectrum of biological activities, including anticancer. The anticancer mechanisms of flavonoids are reported in close agreement, including the inhibition of cancer cell proliferation, the regulation of cell signal pathway, inducing apoptosis, modulating the expression of oncogenes and tumor suppressor genes as well as inhibiting or reversing the drug resistance activity.Breast cancer is the most common malignant among women, most patients have recurrent disease, especially distant recurrences, and drug resistance. The drug efflux proteins of ABC transporter family pump out drugs via active transport to limit the concentration of drugs in cells, this action are associated with drug resistance. BCRP, also named ABCG2, is a new member of the ABC transporter family, and BCRP-overexpression was found in most cancers which appeared mitoxantrone, doxorubicin and daunorubicin resistance.In this study, we evaluated 12 flavonoids(including flavonoid aglycones and their glycosides) on cell proliferation by MTT assay, cell lines included breast cancer MCF-7L, MDA-MB-231, liver cancer SMCC-7721, colon cancer HCT-15. Meaning while, the cellular morphology changes were observed by optical microscopy. the luteolin treated MDA-MB-231 was significantly inhibited after 72 hours (IC₅₀=56.67μM, SMCC-7721: IC₅₀=72.92μM). We also compared the proliferation inhibitory activity of luteolin and 5-fluorouracil at the same concentration, on both cancer cells (MDA-MB-231, SMCC-7721) and their normal cells (HBL-100, L-02). The results demonstrated that luteolin was less effective but almost no cytoxity. We compared the structure and activity relationships(SARs) based on the different activities of 12 flavonoids, 6-hydroxylation on ring B significantly increased the inhibitory activity, the results provide a clue for us modulating the structure of flavonoids to inhibit the proliferation of cancer cells more efficiently.We constructed pcDNA3.1+/bcrp recombinant vector, then successfully transfected breast cancer cell MDA-MB-453, hopefully to pick out stable MDA-MB-453/BCRP cell line overexpressing BCRP to provide material for further study and to screen drugs targeting BCRP.