It is estimated that 20-60% of cancer patients utilize some form of alternative medicine. Plant products play a major role in complimentary medicine. Azadirachta indica tree commonly known as neem has been known for centuries to possess medicinal properties like immunomodulatory, anti-inflammatory, antimutagenic, and anticarcinogenic. We have previously shown that A. indica leaf extract has potent anticarcinogenic capabilities in N-methyl-N-nitrosurea (MNU)-induced mammary cancer model. The aim of our study is to explore the molecular pathways through which A. indica induces mammary tumor regression. Seven week old female Lewis rats were administered MNU. On the appearance of the first palpable tumor the rats were divided into groups receiving different doses of ethanolic A. indica leaf extract (ALE): group 1 control, no treatment; group 2 0.125mg/day; group 3: 0.250mg/day; group 4: 0.500mg/day; group 5: 1mg/day. Treatment was daily for 4 weeks intraperitoneally. The animals were euthanized 12 weeks after the termination of treatment and mammary tumor tissue samples were snap frozen and also fixed in formalin. To analyze key gene expression changes we performed pathway focused PCR microarrays for apoptosis, PI3-Kinase, and angiogenesis signaling pathways. Our results show that ALE induces tumor regression, decreases tumor volume, and inhibits mammary tumor growth by altering specific molecular pathways, linked to the stimulation (Bax, caspases) and inhibition (Bcl-2, CDC42)of apoptosis, up-regulation of tumor suppressor genes (PTEN), down-regulation of proto-oncogene Jun, and inhibition of cell survival (Foxg1, BTK, Akt). ALE treatment down-regulated genes fundamental to migration, adhesion and proliferation of tumor cells (EFNA1, Hif1a). Timp1 (TIMP family matrix metalloproteinase inhibitor) and cyclin D1 expression exhibited a clear dose response. Our data indicates that ALE treatment inhibits mammary tumor development by altering apoptosis, PI3-Kinase and angiogenesis pathways. In conclusion, ALE could be used as a novel complimentary agent that offers anticarcinogenic effects against breast cancer and could also be used along with the current standard treatment options.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4238. doi:10.1158/1538-7445.AM2011-4238