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Figure 6: A schematic diagram summarizing the cytotoxic effects of phytol in human gastric adenocarcinoma AGS cells. Phytol increases ROS levels, which results in the induction of autophagy. ROS-induced Nrf2 enhances the expression of the antioxidant genes and p62. In turn, p62 protein associates with Keap1 (Jain et al., and Komatsu et al.) and activates Nrf2, completing a positive feedback loop (red arrow). Increased p62 levels can induce autophagy in AGS cells, and also has a protective role against phytol-induced apoptosis. Therefore, the induction of apoptosis by phytol treatment can be enhanced by targeting ROS generation or inhibiting the protective autophagy. ROS, Reactive oxygen species; Nrf2, Nuclear factor-erythroid 2-related factor 2; NAC, N-acetyl- L-cysteine; CQ, Chloroquine. |