Tre1 says when, and where, to go

out blow. They found that inhibitors of the earliest stages of autophagosome formation had no effect, but the anti-malaria drug chloroquine, which inhibits the degradative function of autolysosomes, dramatically increased cell death. Affected cells accumulated grossly distorted autophagic vacuoles, lost their mitochondrial membrane potential almost completely, and suffered a large increase in reactive oxygen species within the cell, both a consequence of incomplete organelle destruction. The authors suggest that preventing digestion of autophagosome contents might help kill the cancer cells because the accumulating toxic debris could leak out. Whatever the reason, when tumors received this one-two punch of Akt suppression and chloroquine-induced autophagy disruption, tumor remission was substantially increased. Degtyarev, M., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200801099.