Structurally Related Cytotoxic Effects of Flavonoids on Human Cancer Cells in Vitro

Flavonoids exist extensively in the human diet, and a variety of health effects have been ascribed to them. The cytotoxic effects of 23 flavonoids on breast cancer cells (MDA-MB-231 and MCF-7), colorectal carcinoma cells (LoVo and DLD-1) and prostatic cancer cells (PC3) were investigated. By comparing the cytotoxicity (EC(50)) of selected molecules that differ in only one structure element, we identified several structural properties associated with enhanced cytotoxicity, including the presence of the 2,3-double bond, appropriate hydroxyl numbers, 3-OH, 6-OH and ortho-hydroxylation in ring B. Flavonoids with a 5-OH exhibited lower cytotoxicity than their non-hydroxylated counterparts. Results indicated that 3,6-dihydroxylflavone showed the most potent cytotoxic effect on these cancer cells. The appearance of apoptotic cells with DAPI staining was observed in cancer cells under 3,6-dihydroxylflavone treatment, and the apoptosis analysis by flow cytometry also showed that 3,6-dihydroxylflavone induced apoptotic cell death in these cancer cells. These results revealed the structurally related toxicity of flavonoids on human cancer cells, and indicates that 3,6-dihydroxylflavone is an active compound worthy of development for cancer chemotherapy.