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Inhibition of growth of human small cell lung cancer by bromocriptine
M Ishibashi1, M Fujisawa, H Furue
1Department of Medicine, Teikyo University School of Medicine, Kawasaki, Japan.
Abstract:
Bromocriptine, a dopaminergic agonist, inhibited the growth of human small cell lung cancer (SCLC) implanted as tumor xenografts in athymic nude mice; the effect was dose dependent. In mice bearing a SCLC with ectopic vasopressin production, plasma levels of human vasopressin-associated neurophysin decreased concomitantly. Electron microscopy of tumor tissues revealed marked degenerative changes, including pyknosis, densely aggregated chromatin masses, and vacuolization of cytoplasm after bromocriptine treatment. When a SCLC cell line, NCI-H69, was grown in semisolid medium, bromocriptine inhibited its clonal growth in a dose-related manner. Coincubation with dopamine D2 receptor antagonist, metoclopramide, or domperidone, completely blocked the inhibitory effect of bromocriptine. Receptor studies with a dopamine D2 receptor ligand, [125I]iodosulpride, showed high affinity binding sites on the membranes of SCLC cells. These results indicate that SCLC cells are enriched with dopamine D2 receptors, which may mediate the growth-inhibitory effect of bromocriptine on SCLC. Dopaminergic agonists may be useful in the medical treatment of SCLC.
Insights
Bromocriptine, a dopamine agonist, effectively inhibited small cell lung cancer (SCLC) growth in mice and cell cultures. This suggests dopamine D2 receptors on SCLC cells may be a therapeutic target.
Area of Science:
- Oncology
- Pharmacology
- Neuroendocrinology
Background:
- Small cell lung cancer (SCLC) is an aggressive malignancy with limited treatment options.
- Dopaminergic pathways are increasingly recognized for their role in cancer progression.
Purpose of the Study:
- To investigate the efficacy of bromocriptine, a dopaminergic agonist, in inhibiting SCLC growth.
- To explore the potential role of dopamine D2 receptors in mediating bromocriptine's effects on SCLC.
Main Methods:
- Tumor xenograft models in athymic nude mice were used to assess bromocriptine's effect on SCLC growth.
- In vitro studies evaluated bromocriptine's impact on SCLC cell line clonal growth in semisolid medium.
- Dopamine D2 receptor antagonist (metoclopramide, domperidone) and ligand ([125I]iodosulpride) binding assays were performed.
Main Results:
- Bromocriptine demonstrated dose-dependent inhibition of SCLC tumor xenograft growth.
- Bromocriptine significantly reduced clonal growth of an SCLC cell line in vitro.
- Degenerative changes were observed in tumor tissues following bromocriptine treatment.
- Dopamine D2 receptor antagonists blocked bromocriptine's inhibitory effects, and SCLC cells exhibited high-affinity dopamine D2 receptor binding.
Conclusions:
- SCLC cells express functional dopamine D2 receptors.
- Bromocriptine's growth-inhibitory effect on SCLC is mediated via dopamine D2 receptors.
- Dopaminergic agonists represent a potential therapeutic strategy for SCLC treatment.