Flavonoid C-glucosides Derived from Flax Straw Extracts Reduce Human Breast Cancer Cell Growth In Vitro and Induce Apoptosis.

Key Findings

In plants, flavone-C-glycosides function as antioxidants and possess some favorable activities for humans, as they can protect cells from oxidative stress and counteract inflammation. Flax straw is a source of C-glycosylated flavonoids. In this study, three genetically modified flax types (named W94, GT4, and L9) were generated with increases in phenylpropanoid content: flavonoids (kaempferol and quercetin), anthocyanins, phenolic acids (coumaric, ferulic, and synaptic acids) and lignin. In this study, the in vitro effect of straw extracts from W92, GT, and L and one non-transgenic one (Linola) were tested on the growth, proliferation and apoptosis of cells from the human breast cancer cell line MCF-7. The effects of the pure compounds of the main constituents of flax straw on human breast cancer cells was also tested. The flax straw extracts of different flax types were able to inhibit the proliferation of MCF-7 cells (up to 30%) and were cytotoxic toward this cell line (up to 70% decrease in protein content). The treatment of MCF-7 cells with flavonoid C-glucoside pure compounds reduced the proliferation and was cytotoxic toward human breast carcinoma cells. The results suggest that flax straw extracts inhibit the proliferation of MCF-7 cancer cells by increasing apoptosis.

ABSTRACT

Flax straw of flax varieties that are grown for oil production is a by product which represents a considerable biomass source. Therefore, its potential application for human use is of high interest. Our research has revealed that flax straw is rich in flavonoid C-glucosides, including vitexin, orientin, and isoorientin. The objective of this study was to evaluate the cytotoxicity and possible proapoptotic effect of flax straw derived C-glucosides of flavonoids in the human breast adenocarcinoma cell line (MCF-7). The effects of flax straw derived flavonoid C-glucosides on cell proliferation of MCF-7 cells were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) and sulforhodamine B assays. The expression of apoptosis-related genes was assessed by real-time PCR. Our data revealed that flax C-glucosides as well as pure compounds are cytotoxic toward MCF-7 cells and inhibit their proliferation. Moreover, the induction of apoptosis was correlated with the changes in the mRNA level of pro-apoptotic genes. Increased expression of bax and caspase-7, -8, and -9 and decreased mRNA expression of bcl-2 was observed, whereas the mRNA levels of p53 and mdm2 were not altered. These results clearly demonstrated that flax straw metabolites effectively induced growth inhibition and apoptosis in human breast adenocarcinoma cells.