Evaluation of the anticancer activities of thioflavanone and thioflavone in human breast cancer cell lines

Abstract

Abstract. This study investigated the anticancer effects of thioflavanone and thioflavone in the MCF-7, MDA-MB-231 and MDA-MB-453 human breast cancer cell lines. Cells were treated with either thioflavanone or thioflavone from 1 to 100 µM for 24 h, and their anti-proliferative activity and cytotoxicity was determined. Thioflavanone and thioflavone possessed similar anti-proliferative activities; their IC 50 values were 62-89 and 74-128 µM, respectively, although the cytotoxicity of thioflavanone was significantly higher and occurred in a dose-dependent manner. Taken together, these results suggest that thioflavanone significantly inhibits cellular proliferation with weak cytotoxicity to a greater extent than thioflavone, and induces apoptosis in human breast cancer cell lines. Moreover, thioflavanone, but not thioflavone, induces apoptosis via p53-dependent expression of Bax. IntroductionFlavonoids are a group of over 6,000 phytochemicals that include flavones, flavonols, flavanones, and isoflavones in palnts, and are usually present almost exclusively in the form of β-glycosides. According to several epidemiological studies, flavonoids may reduce the risk of developing cancer and cardiovascular disease (1-3). Due to their benefit to human health, the biological activity of flavonoids has been extensively examined in terms of their antitumor, anti-inflammatory, and antioxidant capacity in vitro (4,5).The common structural feature of flavonoids is the flavan nucleus, which consists of 15 carbon atoms arranged in 3 rings (phenylchromanone structure, C6-C3-C6). Rings A and B are benzene rings and ring C is a heterocyclic pyran or pyrone. A number of the anticancer mechanisms of flavonoids have been shown to be associated with their structure-activity relationships (SAR) (6). Recently, much research has aimed to understand the relationship between structural modifications and biological activity. In an attempt to increase anticancer activity, the synthesis of new flavonoid analogues has been conducted (7). Moreover, the anticancer activity of these synthetic compounds has been observed in various cancer cell lines in vitro (8-13). We previously reported the production of synthetic flavonoids (14-16) that exert various biological activities in vitro (17). Sulfur-containing flavonoid analogues have activities greater than the molecules from which they were derived. For example, synthetic thioflavopiridols may act as selective CDK1 inhibitors in human tumor cell lines (18). Our previous report (17) suggested that synthetic flavanone derivatives were more potent than flavanone in an antiproliferation assay using human breast cancer cells.In the present study, we investigated the anticancer activities of thioflavanone and thioflavone in vitro. We postulated that thioflavanone and thioflavone, which are synthesized as the thio analogues, may possess greater biological activities than their precursors. Materials and methodsSynthesis of thioflavanone and thioflavone. Treatment of thiosalicylic acid (denoted as 1 in Fig. 1) ...

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