Noscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses.
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.
Ke
Y
Y
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Ye
K
K
Grossniklaus
H E
HE
Archer
D R
DR
Joshi
H C
HC
Kapp
J A
JA
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D000996:Antitussive Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001853:Bone Marrow / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007107:Immune System / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009665:Noscapine / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D013154:Spleen / Q000276:immunology; D044005:Tetrahydroisoquinolines; D013997:Time Factors; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000970:Antineoplastic Agents; D000996:Antitussive Agents; D044005:Tetrahydroisoquinolines; C004697:cotarnine; D009665:Noscapine