Inhibiting autophagy enhances anti-cancer properties of sulforaphane.

Bladder cancer (BC) has an extremely low survival rate due to its tendency to metastasize. The antimalarial drug chloroquine (CQ) can inhibit BC progression and invasiveness by targeting basal autophagy. However, the mechanism by which CQ affects BC is not defined. Here, we revealed that although CQ showed an anticancer effect by reducing the migration and proliferation of the analyzed bladder cancer cells, it increased the expression of ICAM-1, a protein whose expression is associated with higher tumorigenic potential. Sulforaphane (SFN), a well-known ICAM-1 inhibitor, significantly contributed to the enhancement of anticancer effect of CQ, through regulation of both AKT/GSK-3β and mTOR/ULK pathways, which led to effective inhibition of autophagy, reduced proliferation level or inhibition of migration of the analyzed bladder cells. Moreover, regulation of pathways related to autophagy contributed to the reduction of mitochondrial membrane potential and regulation of ROS level. Nevertheless, the level of influence of CQ and SFN on the anticancer effects strongly depended on the molecular basis of the analyzed bladder cell lines. Our data indicate that although CQ exerts antitumor effects on bladder cancer cells, it should be noted that activation of some pro-tumor pathways may be associated with subsequent disease relapse or treatment resistance.