noscapine and cotarnine

Noscapine, a phthalideisoquinoline alkaloid derived from opium, has been used as an oral anti-tussive agent and has shown very few toxic effects in animals or humans. Recently, we reported that noscapine binds stoichiometrically to tubulin and promotes microtubule polymerization. Noscapine causes growth arrest of tumor cells in mitosis and induces apoptosis of tumor cells in vitro. Previous experiments also showed that noscapine has potent antitumor activity in mice when administered parenterally or by gastric lavage. Here, we report that the anti-mitotic effect was specific to noscapine since closely related compounds did not inhibit the growth of a lymphoma cell line. In addition, noscapine was shown to be effective in reducing the growth of the lymphoma and increasing the survival of tumor-bearing mice when administered in the drinking water. It is noteworthy that, noscapine showed little or no toxicity to kidney, liver, heart, bone marrow, spleen or small intestine at tumor-suppressive doses. Furthermore, oral noscapine did not inhibit primary immune responses, which are critically dependent upon proliferation of lymphoid cells. Thus, our results indicate that noscapine has the potential to be an effective chemotherapeutic agent for the treatment of human cancer.

Topics: Alkaloids; Animals; Antineoplastic Agents; Antitussive Agents; Apoptosis; Bone Marrow; Cell Division; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Immune System; In Situ Nick-End Labeling; Lymphoma; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Noscapine; Spleen; Tetrahydroisoquinolines; Time Factors; Tissue Distribution; Tumor Cells, Cultured

Noscapine, narcotoline and cotarnine were quantified in deproteinized plasma samples by using a coupled-column liquid chromatographic system. The drug and the metabolites were first separated into two groups on a short polar precolumn (-CN) with an acidic mobile phase, containing a low content of acetonitrile. The metabolites were transferred to a hydrophobic analytical column (C18) and separated with a mobile phase containing a counter ion and a co-ion in an acidic buffer with an high acetonitrile content. Noscapine was transferred to another hydrophobic analytical column (C18) with a mobile phase containing a counter ion in an acidic buffer with an high acetonitrile content. Ultraviolet detection at 310 nm was used for all three compounds. The limits of quantitation were 9 ng/ml for noscapine, 13 ng/ml for cotarnine and 20 ng/ml for narcotoline. The within-day precisions were better than 6% (relative standard deviation), and the absolute recoveries were above 82%.

Topics: Alkaloids; Chromatography, High Pressure Liquid; Electrochemistry; Humans; Mass Spectrometry; Noscapine; Tetrahydroisoquinolines

Topics: Alkaloids; Benzylisoquinolines; Hydro-Lyases; Noscapine; Polarography; Tetrahydroisoquinolines