Dihydroaustrasulfone Alcohol Induces Biphasic Autophagy and Apoptosis in Leukemia Cells via PI3K/Akt and JNK Signaling Pathways

BACKGROUND/AIM: , has demonstrated cytotoxic activity against various cancer types. However, its antitumor effects and underlying mechanisms in human leukemia cells remain unknown. This study aimed to investigate the anticancer effects of DA in leukemia cell models and to elucidate its mechanisms of action. MATERIALS AND METHODS: western blot analysis. RESULTS: -phase cell cycle arrest (11.6% at 24 h; 39.9% at 48 h) and enhanced apoptosis, as evidenced by increased Bax and PARP-1 cleavage and decreased Bcl-2 expression. At 24 h, DA temporarily induced autophagy, as shown by elevated LC3-II/LC3-I ratios and reduced p62 and Atg5 levels; however, autophagic flux was suppressed at 48 h. Furthermore, DA inhibited phosphorylation of PI3K p85 at 24 h and activated JNK phosphorylation at both time points. CONCLUSION: DA elicits a biphasic cellular response in U937 leukemia cells, characterized by transient cytoprotective autophagy followed by apoptotic cell death mediated through dysregulation of Bcl-2/Bax and suppression of the PI3K/Akt pathway. These findings indicate that DA is a promising candidate for novel antileukemic therapeutic strategies.