{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:38:08Z","timestamp":1782970688353,"version":"3.54.5"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      antitumorgenic effects were assessed using CellTiter-Blue viability assays and wound-healing assays, while\n                      <jats:italic>in vivo<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the\n                      <jats:italic>in vitro<\/jats:italic>\n                      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\n                      <jats:italic>in vivo<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments. In contrast, all three drugs exhibited little or no antitumorigenic effect on A375 cells in both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments.. These findings further the efforts to repurpose the FDA-approved tricyclic drugs CPZ, AmiT, and ImiP for cancer treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1827698","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:25:28Z","timestamp":1782966328000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Repurposing tricyclic drugs as cancer therapeutics: comparative analysis of antitumorigenic effects of chlorpromazine, amitriptyline and imipramine"],"prefix":"10.3389","volume":"16","author":[{"given":"Joos","family":"Berghausen","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology, Georgetown University Medical Center","place":["Washington, DC, United 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