Triple-negative breast cancer (TNBC), a highly invasive type of cancer, is difficult to treat due to insufficient specific targets and low survival rates. Current therapy often encounters drug resistance or relapse
thus, repurposing existing drugs could revolutionize cancer treatment. This study examined the anticancer effects of the antipsychotics Cariprazine (CAR), Olanzapine (OLZ), and Clozapine (CLZ), and the immunomodulatory potential of CAR, in vitro and in vivo in TNBC models. In vitro, CAR, OLZ, and CLZ significantly inhibited the proliferation of TNBC cells. This inhibition occurred via the induction of mitochondrial apoptosis, G0/G1 cell cycle arrest, and the suppression of autophagy, as evidenced by the down-regulation of Bcl-2, p62, and pAKT
the upregulation of Bax and active caspase 3
the decrease of ΔΨM
and the promotion of cytochrome c release. In addition, CAR inhibited MDA-MB-231 cells migration. In vivo, CAR inhibited tumor growth in the 4T1 xenograft model without causing adverse effects and resulted in the mRNA upregulation caspase 9, p53, p21, and Beclin-1. In addition, CAR influenced the immune response by promoting the production of proinflammatory cytokines TNF-α, IFN-γ, IL-17, and IL-1β and increasing the percentage of TNF-α