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The researchers found that tricyclic antidepressants and related molecules potently induced apoptosis in both chemonaive and chemoresistant SCLC cells in culture, in mouse and human SCLC tumors transplanted into immunocompromised mice, and in endogenous tumors from a mouse model for human SCLC. Stress pathways were activated by the candidate drugs to induce cell death in SCLC cells, at least in part by disrupting autocrine survival signals involving neurotransmitters and their G protein-coupled receptors. Growth of other neuroendocrine tumors was inhibited by the candidate drugs, including pancreatic neuroendocrine tumors and Merkel cell carcinoma.
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