8-(Tosylamino)quinoline inhibits tumour progression through targeting phosphoinositide-3-kinase/Akt pathway.

We examined whether 8-(tosylamino)quinoline (8-TQ), a structural analogue of BAY 11-7082, is able to modulate various tumourigenic responses using various in vitro and in vivo experimental conditions. 8-TQ exhibited the strongest suppressive activity on the proliferation of C6, A431, HeLa and MDA-MB-231 cells with IC550 values ranging from 10 to 30 microM. According to the analysis of level of active caspase-3, and morphologies of C6, HeLa and MDA-MB-231 cells, it was revealed that 8-TQ is able to induce apoptosis. Furthermore, this compound strongly diminished the invasion of MDA-MB-231 cells, the migration of HeLa cells, and the new generation of blood vessels under non-toxic conditions. Reduction of the phospho-form levels of intracellular signalling enzymes by 8-TQ strongly indicated that molecular signalling machineries composed of phosphoinositide 3-kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/Akt and extracellular-signal-regulated kinase (ERK) could be targeted by 8-TQ treatment. Indeed, the specific inhibitors (LY294002 and U0126) of PI3K/PDK1/Akt and ERK showed similar anti-cancer properties to 8-TQ. Finally, 8-TQ intraperitoneally injected suppressed the increase of tumour volume up to 40% compared to vehicle-treated control. Taken together, our results clearly suggest that 8-TQ might have applications as a novel anti-cancer drug or may be served as a lead compound to be further optimized.