FIGURE 6 from Identification and Characterization of a Small Molecule Bcl-2 Functional Converter

Antitumor effects of BFC1108 in an orthotopic breast cancer model. A, BFC1108 inhibits growth of high Bcl-2–expressing MDA-MB-231 TNBC cells in vivo. A total of 10⁶ MDA-MB-231/Bcl-2 cells were implanted in the mammary fat pad of NOD.SCID mice (n = 8 per group). Once palpable tumors were detected, mice were randomized and treated with vehicle or BFC1108 at 100 mg/kg twice a week by intraperitoneal route. Tumor measurements were made with digital calipers twice a week. *, P < 0.05 from day 18 onward. B, The body weights of mice treated with vehicle or BFC1108 in A were measured twice a week. C, Induction of apoptosis of tumor cells by BFC1108 in vivo. Immunofluorescence was performed on frozen tumor sections to determine apoptosis by TUNEL staining. D, BFC1108 induces conformation change of Bcl-2 in tumor tissues. Bcl-2 conformational change was detected by staining with Bcl-2 BH3 antibody. E, Bax activation by BFC1108. Activated Bax was detected using Bax 6A7 antibody in tumor tissues from animals treated with vehicle or BFC1108. F, Activation of caspase-3 by BFC1108. Activated caspase-3 was detected using cleaved caspase-3 antibody in tumor tissues from animals treated with vehicle or BFC1108.