Supplementary Figures 1 through 10, Supplementary Tables 1 and 2, an Supplementary Materials and Methods from Novel Cancer Therapeutics with Allosteric Modulation of the Mitochondrial C-Raf–DAPK Complex by Raf Inhibitor Combination Therapy

Supplementary Figures 1-10. Suppl. Fig. 1. The cell death caused by Raf inhibitors in RCC cells in vitro and in vivo. Suppl. Fig. 2.S-G combination therapy synergistically induced C-Raf-dependent cell death. Suppl. Fig. 3.S-G combination therapy induced mitochondrial dysfunction and ROS generation. Suppl. Fig. 4. S-G combination therapy induced ROS-dependent cell death and de-phosphorylation of pDAPKS308. Suppl. Fig. 5. The generation of sorafenib-monotherapy resistant cancer cell lines in vivo. Suppl. Fig. 6.S308 phosphorylation status of DAPK did not affect cell proliferation of cancer cells and knock-down of DAPK attenuated cell death of cancer cells sensitive to S-G combination therapy. Suppl. Fig. 7.S-G combination therapy induced C-Raf/pDAPKS308 complex translocation from the mitochondria to the cytoplasm of A498 cancer cells. Suppl. Fig. 8.S-G combination therapy induced mitochondrial morphological change of cancer cells expressing DAPKS308D.Suppl. Fig. 9.DAPKS308D enhanced PMA induced mitochondrial remodelling. Suppl. Fig. 10. S-G combination therapy induced PP2A dissociation from C-Raf/pDAPKS308 complex concomitant with de-phosphorylation of pDAPKS308. Supplementary Tables 1-2. Supplementary Table 1. Clinical characteristics of the drug-resistant RCC patients whose tumors were primarily cultured into stable cancer cell lines. Supplementary Table 2.Correlation of pDAPKS308 expression with clinical and pathological features of 181 patients with renal cell carcinoma. Supplementary materials and methods - Supplemental Experimental Procedures