Recently, we have reported the induction of apoptosis by 2-amino-4-(3-nitrophenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-NC) in HepG2, T47D and HCT116 cells with low nano molar IC50 values. In this study, anti-proliferative effects of modified 4-aryle-4H-chromenes derivatives; 2-amino-4-(3-bromophenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-BC), 2-amino-4-(3-trifluoromethylphenyl)-3-cyano-7-(dimethylamino)-4H-chromene (3-TFC) and 2-amino-4-(4,5-methylenedioxyphenyl)-3-cyano-7-(dimethylamino)-4H-chromene (4, 5-MC) were investigated in three human cancer cell lines. Compared to 3-NC none of the compounds displayed better anti-proliferative effect, although 3-BC appeared somewhat similar. Therefore 3-NC was selected for further studies. Treatment of HepG2, T47D and HCT116 cells with this compound induced apoptosis as visualized by fluorescence microscopic study of Hoechst 33258 stained cells. Induction of apoptosis was quantified by Annexin V/PI staining using flow cytometry. Western blot analysis also revealed that 3-NC down-regulated the expression of anti-apoptotic protein Bcl2 and up-regulated pro-apoptotic protein Bax, in all of the cell lines. Nonetheless, HepG2 cell line was the most responsive to 3-NC as Bax and Bcl2 showed the most dramatic up and down regulation. Our previous finding that 3-NC down regulates Inhibitor of Apoptosis Proteins (IAPs) and the present observation that Bax is upregulated and Bcl2 is down regulated upon 3-NC treatment, this chromene derivative has the potential to overcome chemotherapy resistance caused by up regulation of these proteins.

Reading habits are thought to play an important role in the emergence of cultural differences in visuo-spatial and numerical tasks. Left-to-right readers show a slight visuo-spatial bias to the left side of space and automatically associate small numbers to the left and larger numbers to the right side of space, respectively. A paradigm that demonstrated an automatic spatial-numerical association involved the generation of random numbers while participants performed lateral head turns. That is, Westerners have been shown to produce more small numbers when the head was turned to the left compared to the right side. We here employed the head turning/random number generation paradigm and a line bisection task to a group of 34 Iranians in their home country. In the participants’ native language (Farsi) text is read from right-to-left, but numbers are read from left-to-right. If the reading direction for text determines the layout of spatial-numerical mappings we expected to find more small numbers after right than left head turns. Yet, the generation of small or large numbers was not modulated by lateral head turns and the Iranians showed therefore no association of numbers with space. There was, however, a significant rightward shift in the line bisection task. Thus, while the current results tie in with the idea that reading habits for text play an important role for cultural differences observed in visuo-spatial tasks, our data also imply that these habits on their own are not strong enough to induce significant horizontal spatial-numerical associations. In agreement with previous suggestions we assume that for the emergence of horizontal spatial mappings a congruency between reading habits for words and numbers is required.