Research Paper Volume 12, Issue 23 pp 24318—24332

Figure 7. Schematic diagram of the mechanism underlying ISO’s anti-HCC effects. ISO exposure activates AMPK and inhibits mTOR signaling in HCC cells, leading to upregulation of Atg5, Beclin-1 and LC3B-II and autophagosome formation (1). ISO-induced cell death is effectively alleviated by autophagy blockade (3-MA; si-Atg5) and further enhanced by autophagy stimulation (RAPA), indicating that autophagy activation contributes to ISO-induced cell death. In parallel, activation of the mitochondrial-dependent intrinsic apoptotic pathway is evidenced by a concomitant increase in cleaved caspase-3, cleaved PARP, and the Bax/Bcl-2 ratio (2).