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Repositioning Antipsychotic Fluphenazine Hydrochloride for Treating Triple Negative Breast Cancer With Brain Metastases and Lung Metastases

Repositioning Antipsychotic Fluphenazine Hydrochloride for Treating Triple Negative Breast Cancer With Brain Metastases and Lung Metastases

Fuyan Xu, Yong Xia, Zhanzhan Feng, Wentao Lin, Qiang Xue, Jinrui Jiang, Xi Yu, Cuiting Peng, Min Luo, Yufei Yang, Yuquan Wei, Luoting Yu

Am J Cancer Res. 2019 Mar 1;9(3):459-478.

PMID: 30949404

Abstract:

Triple negative breast cancer (TNBC) patients have a high risk of brain metastases. This deadly disease represents a major challenge for successful treatment, in part because of the poor ability of drugs to penetrate the blood-brain barrier. Antipsychotic drugs show good bioavailability in the brain, and some of them have exhibited anticancer effects in several cancer types. In this study, we investigated the potential of repurposing fluphenazine hydrochloride (Flu) for the treatment of TNBC and the brain metastases. Our data showed that Flu inhibited survival of metastatic TNBC cells. It induced G0/G1 cell cycle arrest and promoted mitochondria-mediated intrinsic apoptosis in vitro. Pharmacokinetic studies in BALB/c mice showed a brain/plasma drug concentration ratio of Flu above 25 for at least 24 hours after dosing. Flu moderately suppressed tumor growth in a TNBC subcutaneous xenograft mouse model. Importantly, Flu exhibited good anti-metastatic potential in a mouse brain metastasis model with an inhibition rate of 85%. In addition, Flu showed a strong inhibitory effect on spontaneous lung metastasis. Moreover, Flu didn't cause serious side effects in the mice. Taken together, this study prompts further preclinical and clinical investigation into repurposing Flu for treating metastatic TNBC patients, which urgently need new treatment options.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP146565-B	Fluphenazine Hydrochloride		146-56-5	Price

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