The NADPH oxidase inhibitor imipramine-blue in the treatment of Burkitt lymphoma.
Burkitt lymphoma is a rare malignancy arising from B cells. Current chemotherapeutic regimens achieve excellent overall survival rates in children, but less impressive rates in adults. There are cases with poor outcome caused by toxic effects of the therapy, tumor lysis syndrome, or metastatic spread of lymphomas to the central nervous system. Modulators of reactive oxygen species are currently discussed as potential drugs for the treatment of cancer. The NADPH oxidase 4 inhibitor imipramine-blue might satisfy the aforementioned requirements, and was studied here. We used MTT assay, crystal violet assay, and thymidine 3H-incorporation assay to analyze the effects of imipramine-blue on Burkitt lymphoma (BL2, BL2B95, BL30B95, BL41B95), neuroblastoma (KELLY, SH-SY5Y, SMS-KAN), cervix carcinoma (HeLa), breast cancer (MDA-MB231), angiosarcoma (AS-M), human embryonic kidney (HEK293WT), and nonmalignant (FLP1) cell lines. The effects of imipramine-blue on BL2B95 cells in vivo were investigated in xenografts on the chick chorioallantoic membrane (CAM). We report that imipramine-blue is a potent growth inhibitor for several cancer cell lines in vitro with IC(50) values comparable to those of doxorubicin (0.16-7.7 μmol/L). Tumor size of BL2B95 cells inoculated in the CAM was reduced significantly (P < 0.05) after treatment with 10 μmol/L imipramine-blue. Lymphogenic dissemination of BL2B95 and the formation of blood and lymphatic vessels in experimental tumors were not affected. We show that imipramine-blue can be used to decrease the viability of cancer cell lines in vitro and in vivo. Imipramine-blue reduces the size of experimental Burkitt lymphoma significantly but does not affect the dissemination of BL2B95 cells, angiogenesis, and lymphangiogenesis.
Authors' Affiliations: Departments of Anatomy and Cell Biology and Hematology and Oncology, University Medicine Goettingen, Goettingen, Germany.
Marcel
M
Klingenberg
Jürgen
J
Becker
Sonja
S
Eberth
Dieter
D
Kube
Jörg
J
Wilting
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000473:pathology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007099:Imipramine / Q000494:pharmacology* / Q000627:therapeutic use; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D009374:Neoplasms, Experimental; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D019255:NADPH Oxidases; D007099:Imipramine