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Antitumor effects of dopaminergic blockers in mice bearing Ehrlich tumors
R Frussa-Filho1, C G Soares, R C Décio
1Departamento de Farmacologia, Escola Paulista de Medicina, São Paulo, Brasil.
Abstract:
We determined the effect of 13 days of treatment with 2.0 mg/kg haloperidol, 30.0 mg/kg metoclopramide or 4.0 mg/kg domperidone on the number of tumor cells of mice bearing Ehrlich ascites carcinoma. The three dopaminergic blockers significantly reduced the number of tumor cells of experimental mice. The mean +/- SEM number of tumor cells x 10(6)/ml saline lavage was 25.5 +/- 5.9 for the haloperidol group, 36.8 +/- 4.7 for the metoclopramide group, 25.3 +/- 3.5 for the domperidone group and 54.0 +/- 9.0 for the control mice (treated with 0.9% NaCl). In a second experiment, treatment with 0.5 and 2.0 mg/kg haloperidol showed that the antitumor effect of this drug was dose dependent. The possible mechanisms underlying these results (such as an increase in prolactin levels or a direct action of these drugs on lymphocytes) are discussed in light of the specific pharmacological properties of each dopaminergic blocker.
Insights
Dopaminergic blockers like haloperidol, metoclopramide, and domperidone significantly reduced tumor cells in mice with Ehrlich ascites carcinoma. The antitumor effect of haloperidol was also found to be dose-dependent.
Area of Science:
- Pharmacology
- Oncology
- Immunology
Background:
- Ehrlich ascites carcinoma is a common model for studying tumor growth.
- Dopaminergic blockers are known to have various physiological effects.
- The potential of these blockers in cancer treatment is an area of interest.
Purpose of the Study:
- To investigate the impact of haloperidol, metoclopramide, and domperidone on tumor cell proliferation in mice.
- To determine if the antitumor effect of haloperidol is dose-dependent.
Main Methods:
- Mice bearing Ehrlich ascites carcinoma were treated for 13 days with haloperidol, metoclopramide, or domperidone.
- Tumor cell counts were measured in saline lavage.
- A dose-response study was conducted for haloperidol.
Main Results:
- All three dopaminergic blockers significantly reduced tumor cell counts compared to controls.
- Haloperidol at 2.0 mg/kg resulted in 25.5 +/- 5.9 x 10(6) tumor cells/ml.
- Metoclopramide (30.0 mg/kg) showed 36.8 +/- 4.7 x 10(6) tumor cells/ml, and domperidone (4.0 mg/kg) showed 25.3 +/- 3.5 x 10(6) tumor cells/ml.
- Lower doses of haloperidol also demonstrated an antitumor effect, indicating dose dependency.
Conclusions:
- Haloperidol, metoclopramide, and domperidone exhibit significant antitumor activity against Ehrlich ascites carcinoma in mice.
- The findings suggest potential therapeutic applications for these dopaminergic blockers in cancer treatment.
- Further research is warranted to elucidate the precise mechanisms, possibly involving prolactin levels or direct lymphocyte interactions.