Crocin reproduced the MACC1-dependent effect of saffron. Cells were treated with different crocetin concentrations. Crocetin did not reduce the proliferation of both MACC1 high and low expressing cells (A,B). Safranal reduced the proliferation rate of both cell lines in a MACC1-independent manner (C,D). Crocin decreased the proliferation rate of the CRC cells with high MACC1 level (E,F). In addition, migration reduction in high MACC1-expressing CRC cells was observed under crocin treatment in Boyden chamber assay (G). Following this, via chromatography analysis, the direct read of crocin extract of each saffron was established. High variation of crocin has been observed between the four different saffron extracts (H). Data are represented as mean ± SEM (n ≥ 3). p values were calculated using Student’s t-test. * p < 0.05.