Fig. 7

Bupropion as a repurposed drug for anti-metastasis in breast cancer. a Binding model between nicotinic acetylcholine receptor subunit α9 (CHRNA9), bupropion, and nicotine. Compared with nicotine, the 1-(3-chlorophenyl)propan-1-one bupropion moiety can bind an additional subpocket comprising several CHRNA9 contact residues (e.g., I140, G141, S142, and D194). b Bupropion as an inhibitor attenuating nicotine-induced CHRNA9/ERBB2 dissociation, as detected by an immunoprecipitation (IP) assay. BT474 cells exposed with or without 10 μM nicotine were subjected to bupropion pretreatment at 0, 0.1, and 1 μM. An ERBB2 antibody/bead complex was precipitated and immunoblotted for a CHRNA9 antibody, and an ERBB2 blotting was used as the loading control. Bupropion as a repurposed drug not only inhibits the c, d migration and e, f invasion abilities of BT474 (24 and 72 h) and MDA-MB-231 (12 and 48 h) cells, and g the metastasis ability of a spontaneous pulmonary metastasis mouse model but also attenuates the nicotine-induced effects. In invasion and migration assays, the cells were either treated with or without nicotine (10 µM). All mice were randomized into six groups (n = 5 per group) and intraperitoneally injected with phosphate-buffered saline, 100 or 200 µg kg⁻¹ bupropion three times per week, and with or without nicotine treatment (10 μg ml⁻¹) via their drinking water. After 2 months, the mice were sacrificed, and their lung tissues were measured for metastasis by bioluminescence imaging. The color bar indicates a signal gradient from high (red) to low bioluminescence intensity (blue). The error bars indicate the mean ± standard error. Data were analyzed with Student’s t tests; all P values were two-sided. P values <0.05 and <0.01 are indicated by an asterisk and double asterisk, respectively. Source data are provided as a Source Data file