Anticancer and antimicrobial activities of diosmin

Abstract

Flavonoids are a group of natural polyphenols that are typically present in many higher plants as secondary metabolites with low molecular weight. Diosmin (3′,5,7-trihydroxy-4′-methoxyflavone-7-ramnoglucoside) is a naturally occurring flavonoid found in relatively large quantities in citrus fruits. We examined the cytotoxic, antiangiogenic and antimicrobial activity of diosmin. The cytotoxic effect was assessed by the WST-1 test. Cellular DNA fragmentation was determined by measuring BrdU-labeled DNA fragments. The mRNA and protein levels were assessed by qRT-PCR and Western blot. The minimal inhibitory concentrations (MIC) of diosmin for six Gram-positive and nine Gram-negative bacteria were determined by using a microdilution method. Diosmin significantly and selectively inhibited proliferation depending on concentration and exposure time. Following diosmin treatment of MDA-MB-231 cells, a concentration-dependent and time-dependent increase in the number of apoptotic BrdU-labeled DNA fragments was observed. Exposure of MDA-MB-231 breast cancer cells to diosmin for 24 h markedly increased the mRNA expression of Bax and caspase-3, whereas the expressions of Bcl-2 and Bcl-XL were decreased. Furthermore, Western blotting demonstrated that protein expression of Bcl-2 and Bcl-XL was downregulated, while the expression of Bax and caspase-3 proteins was upregulated. Based on the MICs, significant activity was only seen against Gram-positive bacteria. We conclude that diosmin is a potential candidate for use in the treatment of breast cancer and for controlling infection.