Figure 7. DLBCLs and RCCs Are Sensitive to GPX4-Regulated Ferroptosis.

(A) Testing erastin in 117 cancer cell lines revealed DLBCLs as a cancer subtype susceptible to ferroptosis. DLBCL cell lines are marked with lines on the left. The table shows the name of DLBCL cell lines along with the sensitivity rank.

(B) DLBCLs were more sensitive to erastin than AML and MM cells.

(C) DLBCL cell lines are no more sensitive to lethal compounds than other hematopoietic cell lines. The total number of AUCs in the analysis was 3,883 (972 for DLBCL and 2,911 for other hematopoietic cell lines).

(D and E) DLBCL cells died through a mechanism characteristic of ferroptosis, as determined by lipid peroxide generation and death rescue by Vit. E.

(F) Sensitivity profile of 53 cancer cell lines in the “NCI60” cell panel against erastin. The cell lines were grouped based on their tissue origins.

(G) The eight RCC cell lines were retested with erastin to confirm their sensitivity against erastin.

(H) Erastin and RSL3 generated lipid ROS in the two RCC cell lines.

(I) Cell death was rescued by a lipophilic antioxidant, Vit. E.

(J) GPX4 depletion by siGPX4 induced cell death in RCC cell lines. The western blot (right) confirmed expression of GPX4 protein in these RCC cell lines and knockdown of GPX4 by siRNAs. Scale bars, 30 μm.

(K) Ferroptosis inhibitors suppressed cell death induced by GPX4 knockdown but could not suppress cell death induced by the control siRNAs (siDeath) that kill cells via a nonferroptotic pathway.

Data points in (E), (G), and (I)–(K) represent mean ± SD (n = 3). **p < 0.01; ***p < 0.001. See also Figure S7 and Table S5.