The Effects Of CMFT On Cytotoxicity And Gene Expression Profiles In Vitro

Thiochromanones with unsaturated cyclic ketone as the main structure, have extensive biological activities, like anti-bacterial, anti-inflammatory, anti-tumor and so on.3-chloromethylene-6-fluorothiochroman-4-one(CMFT) is a kind of the thiochromanones derivatives that owns better anti-tumor activities. Studies found that this material has the cis-trans isomers, in this paper the anti-tumor activity of the cis-trans isomers was compared,and the gene expression profiles of the tumor cells, which were affected by cis-3-chloromethylene-6-fluorothiochroman-4-one, were tested as well.The cis-trans isomers activity comparison was determined by MTT colorimetric analysis,and chose Hela, Hep G-2, Raw264.7 and BV2 as tested tumor cells, cisplatin as positive control. The gene expression profiles of the tumor cells were detected by gene chip technology, and chose Hela, Raw264.7 as the subjects, DMSO group as negative control. The experimental results showed that the trans-isomer of CMFT has significant antitumor activity,and can significantly inhibit the proliferation of the four tumor cells, and also behave in concentration dependence; while cis isomer was not so significant, and showed anti-tumor activity only in relatively high concentration. Gene expression profile analysis results showed that ratio of the increased gene expression is bigger than that of the decreased gene when CMFT acted on two tumor cells; and the ratio of gene expression changes of Hela is more obvious. Obvious gene expression changes contain both apoptosis-promoting gene and apoptosis-suppressing gene, but apoptosis-promoting gene expression is more apparent, thus,CMFT can inhibit the tumor cells. Studies have shown that CMFT can induce the production of TNF-α, this experiment detected the production of another cytokine─NO by Griess method.Different solvent can dissolve different compounds, we selected DMSO and polyethylene glycol(peg) 200 to study the solvent effect on the drug.This study suggests that anti-tumor activity of CMFT trans-isomer is more significant,and the structure is more stable; gene expression profiles show that the apoptosis-promotingeffect of CMFT on tumor cells is more apparent, and then induce the apoptosis; CMFT could slightly induce the production of NO in BV2 and Raw264.7; the anti-tumor effect of3-chloromethylene-6-methyl-4-one(CMMT) dissolved by DMSO was more efficient, and the cisplatin could inhibit more tumor cells when dissolved by polyethylene glycol(peg) 200.