Previously, it has been reported that SFN at 15 μM concentration caused accumulation of MCF-7 and MDA MB 231 cells in G2/M phase of the cell cycle after 24 h treatment and longer incubation time resulted in apoptosis initiated by mitochondrial or death receptor pathway, respectively. Moreover, global HDAC activity, as determined with an in vitro activity assay, was inhibited by SFN in MCF-7, MDA MB 231 and, to a lesser extend, in MDA MB 468 and T47D cell lines [16]. Authors also reported that IC50 of SFN did not differ significantly between these cell lines when treated for 48 h [16]. Increased tubulin acetylation and suppression of microtubules dynamic instability was observed in MCF-7 exposed to 15, 25 or 50 μM SFN [17]. G2/M cell cycle arrest of MDA MB 231 cells was associated with increased p21 and p27 cdk-cyclin inhibitors and decreased levels of cyclin A, B1 and cdc2, and apoptosis was accompanied by decreased Bcl-2 and increased caspase-3 level [31]. The same authors showed that SFN induced autophagy in MDA MB 231 cells and this process played a protective role as its inhibition by bafilomycin A1 significantly enhanced SFN-induced apoptosis [31]. It was also reported that sensitivity of breast cancer cells to SFN is connected with upregulation of p38 MAP kinase and caspase -7 activation in MCF-7 cells [32], global changes in gene expression [33] or downregulation of ER, EGFR or HER2 mRNAs [16, 34]. Other studies indicate that SFN-induced apoptosis of MCF-7 and MDA MB 231 cells is initiated by reactive oxygen species due to p66Shc translocation to mitochondria and collapse of mitochondrial membrane potential [35]. Interestingly, non-tumorigenic human mammary epithelial MCF-10A cells were resistant to SFN-induced oxidative stress and cell death [35]. Thus, it seems that cytotoxic effect of SFN is specific for cancer cells. Other reports confirm it. For instance, human mammary epithelial cell line, MCF-12A, was significantly more resistant to 48-h treatment with SFN comparing to cancer cells, MCF-7 wt and MCF-7/Adr (IC50 = 40.5 μM for MCF-12A as compared to 27.9 μM for MCF-7 wt and 13.7 μM for MCF-7/Adr) [36]. Moreover, 30 μM SFN inhibited MCF-7 and ZR75-1 cancer cells proliferation by 80 % after 48-h exposure, while proliferation of non-tumorigenic mammary cells, MCF-10F, was inhibited by about 50 % as compared to the respective controls [34]. Dose- and time-dependent growth inhibition with SFN was observed in MCF-7 and MDA 231 cells, while MCF-10A epithelial cells were more resistant, even to higher (above 10 μM) SFN concentrations. Interestingly, authors found that SFN-induced apoptosis in breast cancer cells was mediated by epigenetic regulation of telomerase gene expression [37]. None of the above mentioned research explored connection of SFN activity with AktmTOR-S6K1 pathway in breast cancer cells.