Mitochondria are well known for their important roles in oxidative phosphorylation, amino acid metabolism, fatty acid oxidation and ion homeostasis. Although the effects of mitochondrial dysfunction on tumorigenesis in various cancer cells have been reported, the correlation between mitochondrial dysfunction and epithelial‑to‑mesenchymal transition (EMT) in lung cancer development and metastasis has not been well elucidated. In the present study, the effects of mitochondrial dysfunction on EMT and migration in lung cancer cells were investigated using inhibitors of mitochondrial respiration, oligomycin A and antimycin A. Oligomycin A and antimycin A induced distinct mesenchymal‑like morphological features in H23, H1793 and A549 lung cancer cells. In addition, they decreased the expression levels of the epithelial marker protein E‑cadherin, but increased the expression levels of the mesenchymal marker proteins Vimentin, Snail and Slug. The results of immunofluorescence staining indicated that oligomycin A and antimycin A downregulated cortical E‑cadherin expression and upregulated the expression of Vimentin. In addition, oligomycin A and antimycin A increased the migration and invasion of A549 lung cancer cells, and promoted the expression levels of phosphorylated (p)‑protein kinase B (AKT) and p‑AMP‑activated protein kinase (AMPK). Notably, the production of reactive oxygen species by oligomycin A and antimycin A did not affect the expression of EMT protein markers. Conversely, treatment with the AKT inhibitor wortmannin and the AMPK inhibitor Compound C upregulated E‑cadherin and downregulated Vimentin expression. These results suggested that oligomycin A and antimycin A may induce migration and invasion of lung cancer cells by inducing EMT via the upregulation of p‑AKT and p‑AMPK expression.

A prior study identified that 4-O-methylascochlorin (MAC), a methylated derivative of ascochlorin (ASC) from the fungus Ascochyta viciae, activates autophagy in leukemia cells by suppressing c-Myc phosphorylation. However, the effects of MAC on autophagy in other cancer cells remain unknown. In the present study, we demonstrated that MAC activated autophagy in human glioblastoma. MAC increased expression of autophagy-related proteins, such as LC3-II and Beclin-1. Moreover, MAC stimulated AMP-activated protein kinase (AMPK) phosphorylation and suppressed phosphorylation of the mTOR, p70S6K, and 4EBP1. The well-known AMPK activator metformin increased LC3-II levels, which were augmented by MAC cotreatment. AMPK knockdown decreased LC3-II levels and inhibited MAC activation of autophagy. Furthermore, MAC suppression of c-Myc expression activated autophagy. Treatment with the c-MYC inhibitor, 10058-FA, induced autophagy, as did c-Myc small interfering RNA knockdown. These effects were augmented by MAC cotreatment. Taken together, these findings indicated that MAC induces autophagy in human glioblastoma by activating AMPK signaling and inhibiting c-Myc protein expression in human glioblastoma.