Inhibition of growth of human small cell lung cancer by bromocriptine

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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1994-07, Vol.54 (13), p.3442-3446
Main Authors: ISHIBASHI, M, FUJISAWA, M, FURUE, H, MAEDA, Y, FUKAYAMA, M, YAMAJI, T
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Bromocriptine - administration & dosage
Bromocriptine - pharmacology
Carcinoma, Small Cell - blood
Carcinoma, Small Cell - chemistry
Carcinoma, Small Cell - pathology
Carcinoma, Small Cell - prevention & control
Cell Division - drug effects
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
General aspects
Humans
Lung Neoplasms - blood
Lung Neoplasms - chemistry
Lung Neoplasms - pathology
Lung Neoplasms - prevention & control
Medical sciences
Mice
Mice, Nude
Pharmacology. Drug treatments
Receptors, Dopamine - analysis
Transplantation, Heterologous
Vasopressins - secretion
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Summary: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.
ISSN:0008-5472
1538-7445