The antipsychotic agent trifluoperazine suppresses triple-negative breast cancer tumor growth and brain metastasis
The antipsychotic agent trifluoperazine hydrochloride suppresses triple-negative breast cancer tumor growth and brain metastasis by inducing G0/G1 arrest and apoptosis https://www.nature.com/articles/s41419-018-1046-3
Women with aggressive triple-negative breast cancer (TNBC) are at high risk of brain metastasis, which has no effective therapeutic option partially due to the poor penetration of drugs across the blood−brain barrier. Trifluoperazine (TFP) is an approved antipsychotic drug with good bioavailability in brain and had shown anticancer effect in several types of cancer. It drives us to investigate its activities to suppress TNBC, especially the brain metastasis. In this study, we chose three TNBC cell lines MDA-MB-468, MDA-MB-231, and 4T1 to assess its anticancer activities along with the possible mechanisms. In vitro, it induced G0/G1 cell cycle arrest via decreasing the expression of both cyclinD1/CDK4 and cyclinE/CDK2, and stimulated mitochondria-mediated apoptosis. In vivo, TFP suppressed the growth of subcutaneous xenograft tumor and brain metastasis without causing detectable side effects. Importantly, it prolonged the survival of mice bearing brain metastasis. Immunohistochemical analysis of Ki67 and cleaved caspase-3 indicated TFP could suppress the growth and induce apoptosis of cancer cells in vivo. Taken together, TFP might be a potential available drug for treating TNBC with brain metastasis, which urgently needs novel treatment options.
Many Thanks Daniel for sharing this. I recall in your another section on Increasing effectiveness of Chemo
One anti-psychotic drug, Aripiprazole which is listed to inhibit Multi Drug Resistance is also there. Not sure but there might be some similarity in action between both these anti-psychotics. In that regard, I remember (don't hv the link handy) that Propranolol also inhibits bone and brain metastatic activity in breast cancer (in vivo).
Kudos to your great work