Neem (Azadirachta indica) leaf mediated immune activation causes prophylactic growth inhibition of murine Ehrlich carcinoma and B16 melanoma

Conditional growth inhibition of murine Ehrlich carcinoma (EC) and B16 melanoma (B16Mel) was observed, following treatment of mice (Swiss and C57BL/6) with aqueous extract of neem (Azadirachta indica) (1 unit/mice/week for 4 weeks) either before or after inoculation of 1 x 10(6) tumor cells. Tumor inoculation after weekly injections for 4 weeks with neem leaf preparation (NLP) induced significant reduction of tumor growth (both EC and B16Mel) and increased survivability of mice. On the other hand, NLP treatment after tumor inoculation demonstrated no tumor growth inhibition in the NLP treated group in comparison to the PBS treated control. No direct cytotoxic effect of NLP towards EC and B16Mel tumor cells was observed in vitro. The spleen cells of NLP treated mice when mixed with inoculum of B16Mel tumor cells and injected into a group of mice, tumor growth was found to be significantly reduced and survivability of the tumor hosts increased remarkably in comparison to mice inoculated with tumor along with normal spleen cells. Concanavalin A (ConA) induced proliferation of lymphocytes from NLP treated mice was significantly higher than the lymphocytes of untreated mice. In in vitro, NI-P by itself had no proliferative effects on lymphocytes but it co-stimulated ConA induced mitogenesis. NLP induced lymphocytosis as evidenced by increased lymphocyte count in blood as well as spleen. Flow cytometric evidence suggested that increase in CD4+ and CD8+ T cells accounted for lymphocytosis. The conditional tumor growth retardation, observed in mice treated with NI-P before tumor inoculation, may be regulated by NLP mediated immune activation, having prominent role in the cellular immune function of the tumor host. (C) 2004 Elsevier B.V. All rights reserved.