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Research Article: Repurposing tricyclic drugs as cancer therapeutics: comparative analysis of antitumorigenic effects of chlorpromazine, amitriptyline and imipramine

Date Published: 2026-07-02

Abstract:
Tricyclic drugs such as chlorpromazine (CPZ), amitriptyline (AmiT), and imipramine (ImiP) have demonstrated antitumorigenic potential, yet their relative potency and selectivity for different tumors remain unclear. Here, we conducted a comparative study of the antitumorigenic effects of these drugs on three major cancer types: breast cancer (MDA-MB-231), neuroblastoma (SH-SY5Y), and melanoma (A375). In vitro antitumorgenic effects were assessed using CellTiter-Blue viability assays and wound-healing assays, while in vivo effects were evaluated using zebrafish xenografts. Cancer cell growth inhibition and migration were examined across all three cancer cell lines following treatment with CPZ, AmiT, or ImiP. In the in vitro experiments, inhibition of cancer cell growth was strongest for CPZ and weakest for ImiP, with AmiT showing intermediate effects across all three cell lines. In wound-healing assays, all three drugs significantly impaired migration in MDA-MB-231 and SH-SY5Y cells but had no effect on the migration of A375 cells. In the in vivo experiments, CPZ and AmiT significantly reduced tumor growth in MDA-MB-231 and SH-SY5Y xenografts, whereas ImiP inhibited tumor growth in a statistically significant manner only for MDA-MB-231 xenografts and did not inhibit tumor growth in SH-SY5Y xenografts. All three drugs failed to inhibit tumor growth in A375 xenografts. Together, these findings demonstrate clear differences in antitumorigenic potency and cancer-type sensitivity among the tested tricyclic drugs, with CPZ being the most potent in both MDA-MB-231 and SH-SY5Y cells, followed by AmiT and then ImiP, in both in vitro and in vivo experiments. In contrast, all three drugs exhibited little or no antitumorigenic effect on A375 cells in both in vitro and in vivo experiments.. These findings further the efforts to repurpose the FDA-approved tricyclic drugs CPZ, AmiT, and ImiP for cancer treatment.

Introduction:
Tricyclic drugs such as chlorpromazine (CPZ), amitriptyline (AmiT), and imipramine (ImiP) have demonstrated antitumorigenic potential, yet their relative potency and selectivity for different tumors remain unclear. Here, we conducted a comparative study of the antitumorigenic effects of these drugs on three major cancer types: breast cancer (MDA-MB-231), neuroblastoma (SH-SY5Y), and melanoma (A375).

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