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The natural product auraptene can influence tumor cell proliferation and invasion, but its effect on hepatocellular carcinoma (HCC) cells is unknown. Here, we report that auraptene can exert anti-tumor effects in HCC cells via inhibition of cell proliferation and ferroptosis induction. Auraptene treatment induces total ROS and lipid ROS production in HCC cells to initiate ferroptosis. The cell death or cell growth inhibition of HCC cells induced by auraptene can be eliminated by the ROS scavenger NAC or GSH and ferroptosis inhibitor ferrostatin-1 or Deferoxamine Mesylate (DFO). Mechanistically, the key ferroptosis defense protein SLC7A11 is targeted for ubiquitin–proteasomal degradation by auraptene, resulting in ferroptosis of HCC cells. Importantly, low doses of auraptene can sensitize HCC cells to ferroptosis induced by RSL3 and cystine deprivation. These findings demonstrate a critical mechanism by which auraptene exhibits anti-HCC effects via ferroptosis induction and provides a possible therapeutic strategy for HCC by using auraptene or in combination with other ferroptosis inducers.

Based on our study of the nature and variation of mineralization-controlling faults in their deep extension and the spatial distribution of gold orebodies in the northwestern Shandong Peninsula （NSP）, here we propose that the gold deposits in the Jiaojia gold belt are controlled by listric faults and the gold deposits in the NSP are controlled by extensional fault system. We also suggest that there is a multiple mineralization space in the deep part of the NSP gold belt. As steps or benches occur along the deep extention of the listric fault where its dipping angle changes from steep to gentle, a number of gold deposits are corre- spondingly distributed as a steplike pattern, which is named as a step metallogenetic model for gold deposits in the NSP. The gold deposits in Shandong Peninsula were formed in the Cretaceous when the crust in the region experienced extention and thinning following the strong collision between North China Plate and Yangtze Plate during the Triassic. Crust anataxis, fluid remobilization, and extention-detachement of the crust are the leading factors for the gold mineralization.