Plant-based medicines are useful in the treatment of
cancer. Many
breast cancer patients use complementary and
alternative medicine in parallel with conventional treatments. Neem is historically well known in Asia and Africa as a versatile medicinal plant with a wide spectrum of
biological activities. The experiments reported herein determined whether the administration of an ethanolic fraction of Neem leaf (EFNL) inhibits progression of chemical
carcinogen-induced mammary
tumorigenesis in rat models. Seven-week-old female Sprague Dawley rats were given a single
intraperitoneal injection of
N-methyl-N-nitrosourea (MNU). Upon the appearance of palpable mammary
tumors, the rats were divided into vehicle-treated control groups and EFNL-treated groups. Treatment with EFNL inhibited MNU-induced mammary
tumor progression. EFNL treatment was also highly effective in reducing mammary
tumor burden and in suppressing mammary
tumor progression even after the
cessation of treatment. Further, we found that EFNL treatment effectively upregulated proapoptotic genes and
proteins such as p53, B cell lymphoma-2
protein (Bcl-2)-associated X
protein (Bax), Bcl-2-associated death promoter
protein (Bad)
caspases,
phosphatase and
tensin homolog gene (PTEN), and
c-Jun N-terminal kinase (JNK). In contrast, EFNL treatment caused downregulation of anti-apoptotic (Bcl-2),
angiogenic proteins (
angiopoietin and
vascular endothelial growth factor A [
VEGF-A]),
cell cycle regulatory proteins (
cyclin D1,
cyclin-dependent kinase 2 [Cdk2], and Cdk4), and pro-survival signals such as NFκB,
mitogen-activated protein kinase 1 (MAPK1). The data obtained in this study demonstrate that EFNL exert a potent anticancer effect against mammary
tumorigenesis by altering key signaling pathways.