CASP3 and neoplasm: Importantly, combined treatment with sorafenib and amiloride increased 4-HNE staining significantly without altering cleaved caspase-3 staining in tumor tissues from SK-Hep1- and Huh7-bearing mice (Fig. 5C and D and Fig. S5E, F), indicating that ferroptosis is responsible for the increased therapeutic effect of sorafenib.