Figure 3.

Anti-cancer activity of the synthetic SAs. Synthetic surfactants demonstrate significant anti-cancer activity through the activation of both intrinsic (BCL, Edelfosine, NP-40) and extrinsic apoptotic pathways (BCL, Edelfosine), unfolded protein response-mediated cell death (Edelfosine) and the suppression of the MAPK/ERK and Akt/PI3K signaling pathways (Edelfosine). Additionally, the synthetic SAAs Edelfosine was shown to inhibit the migration of cancer cells by suppressing the small conductance calcium-activated potassium channel 3 (SK3) activity. Abbreviations: RTK: receptor tyrosine kinase; PI3K: phosphatidylinositol-3-Kinase; MAPK: mitogen-activated protein kinase; ERK: extracellular signal-regulated kinase; MEK: MAPK/ERK kinase; PIP₂: phosphatidylinositol 4,5-bisphosphate; PIP₃: phosphatidylinositol (3,4,5)-trisphosphate; NF-kB: nuclear factor kappa-light-chain-enhancer of activated B cells; FOXO3a: forkhead box O3a; GSK3β: glycogen synthase kinase 3 beta; UPR-mediated cell death: unfolded protein response-mediated cell death; BiP: binding immunoglobulin protein; PERK:protein kinase R-like endoplasmic reticulum kinase; eIF2a: eukaryotic translation initiation factor 2a; ATF4: activating transcription factor 4; CHOP: CCAAT-enhancer-binding protein homologous protein; PARP: poly (ADP-ribose) polymerase; Bid: BH3-interacting domain death agonist; tBid: truncated Bid; Bcl-2: B-cell lymphoma 2; BCL-XL: B-cell lymphoma-extra-large; BAX: BCL2 associated X; BAK: BCL2-antagonist/killer; ROS: reactive oxygen species; Smac/DIABLO: second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI; IAPs: inhibitors of apoptosis proteins; Apaf-1: apoptotic protease activating factor 1; SK3: small conductance calcium-activated potassium channel 3 (SK3); Orai1: ORAI calcium release-activated calcium modulator 1.