Fig. 1

ER stress caused by disruption of autophagy–lysosome flux or conventional chemotherapy confers synergistic therapeutic effects. While p62/SQSTM1 is downregulated during autophagy–lysosome flux, lipidated form of LC-3 (LC-3II) accumulates (lower panel). Obstruction of autophagy flux can be pharmacologically induced by chloroquine, which results in ubiquitination, p62 activation, and LC3-II accumulation (upper panel). Impairment of the autophagy–lysosome pathway induces apoptosis mainly via excessive ER stress. On the other hand, TMZ is an alkylating agent that induces formation of O⁶-methylguanine in DNA, which in turn induces mismatch pair with thymine during the following cycle of DNA replication. Thus, chloroquine and TMZ exhibit the synergistic therapeutic effect for cancer cells