Toxicity, Antitumor and Chemosensitizing Effects of 3-Chloroprocainamide |
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Authors: | Jianyi Hua Ronald W Pero |
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Affiliation: |
a Department of Cell and Molecular Biology, Section for Molecular Ecogenetics, University of Lund, Lund, Sweden |
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Abstract: | 3-chloroprocainamide (3-CPA), an analog of metoclopramide (MCA), dose-dependently inhibited tumor growth in scid mice xenografted with a human brain astrocytoma (T24) when given intramuscularly to mice every third day for 14-20 days. 3-CPA was shown to have the same efficacy on tumor growth inhibition as neutral metoclopramide (neutral MCA) at the doses of 10 40 mg/kg when evaluated by tumor doubling time, tumor growth time for tumor volumes to reach 1 000 mm3 and area under growth curve. 3-CPA at the dose of 3 × 40 mg/kg was also shown to enhance the cytotoxicity induced by a single dose of cisplatin at 7.5 mg/kg. A dose of ± 160 mg/kg of 3-CPA did not show any notable extrapyramidal symptoms which was observed for neutral MCA treated mice at the dose of 20 mg/kg. The lethal response dose of 3-CPA for scid mice was 320 mg/kg which is 4 times higher than that determined for neutral MCA (80 mg/kg). These results support 3-CPA as a good candidate drug representing a new generation of benzamides for further clinical development as a cancer therapy drug. |
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