Cytotoxic effect of three novel thiochromanone derivatives on tumor cell in vitro and underlying mechanism

Yuemin Zhao¹, Chunna Li¹, Haitao Suo¹, Yanping Wang¹, Chunliu Yang^1,2, Zhengyue Ma^1,2 and Yuxin Liu^1,2

¹College of Pharmaceutical Sciences, Hebei University, Baoding, Hebei Province, 071002, P. R. China;

²Drug Quality Control Key Laboratory of Hebei Province, Baoding, Hebei Province, 071002, P. R. China

*Corresponding Author E-mail: yuxinliu@hbu.edu.cn; Tel: (86)186-3026-2196; Fax: (86)0312-597-1107

Accepted 09 September, 2014

Abstract

Thiochromanone derivatives have received extensive attention for their biological activities, but their anti-tumor activities were seldom reported. In this paper, in vitro anti-proliferative activities of three novel thiochromanone derivatives, (z)-3-(chloromethylene)-6-fluorothiochroman-4-one (CMFT), (z)-3-(bromomethylene)-6-fluorothiochroman-4-one (BMFT) and (z)-3-(chloromethylene)-6-chlorothiochroman-4-one (CMCT) were investigated by the method of MTT assay. All the tested chemicals showed cell toxicity to 13 human cell lines (A549, SGC-7901, BGC-823, U937, K562, Hela, MCF-7, HepG-2, A375, LS174T, HT1080, C4-2B and MRC-5), and half maximal inhibitory concentration (IC₅₀) values were between 2.3-36.3 μM. CMFT was chosen as a representative to invested the underlying mechanism. Cell apoptotic ratio was measured by flow cytometry analysis. The results showed that CMFT induced tumor cell apoptosis. Cysteinyl aspartate-specific proteases detection confirmed CMFT increased activity of caspase-8, caspase-9 and caspase-3. Moreover, CMFT could enhance the level of death receptor 3 (DR3). In conclusion, current results suggested novel thiochromanone derivative CMFT could kill tumor cells by inducing tumor cell apoptosis via increasing apoptosis-related factors.

Keywords Thiochromanones; antiproliferation; apoptosis; caspases; tubulin.