title: Neem leaf extract inhibits mammary carcinogenesis by altering cell proliferation, apoptosis, and angiogenesis.
abstract: 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.
authors.affiliation: Center of Excellence in Cancer Research; Department of Biomedical Sciences; Texas Tech University Health Sciences Center; Paul L Foster School of Medicine; El Paso, TX USA.
authors.forename: Arunkumar
authors.initials: A
authors.lastname: Arumugam
authors.affiliation: Center of Excellence in Cancer Research; Department of Biomedical Sciences; Texas Tech University Health Sciences Center; Paul L Foster School of Medicine; El Paso, TX USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Agullo
authors.affiliation: Center of Excellence in Cancer Research; Department of Biomedical Sciences; Texas Tech University Health Sciences Center; Paul L Foster School of Medicine; El Paso, TX USA.
authors.forename: Thiyagarajan
authors.initials: T
authors.lastname: Boopalan
authors.affiliation: Center of Excellence in Cancer Research; Department of Biomedical Sciences; Texas Tech University Health Sciences Center; Paul L Foster School of Medicine; El Paso, TX USA.
authors.forename: Sushmita
authors.initials: S
authors.lastname: Nandy
authors.affiliation: Center of Excellence in Cancer Research; Department of Biomedical Sciences; Texas Tech University Health Sciences Center; Paul L Foster School of Medicine; El Paso, TX USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lopez
authors.affiliation: Center of Excellence in Cancer Research; Department of Biomedical Sciences; Texas Tech University Health Sciences Center; Paul L Foster School of Medicine; El Paso, TX USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Gutierrez
authors.affiliation: Department of Chemistry; University of Texas at El Paso; El Paso, TX USA.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Narayan
authors.affiliation: Center of Excellence in Cancer Research; Department of Biomedical Sciences; Texas Tech University Health Sciences Center; Paul L Foster School of Medicine; El Paso, TX USA.
authors.forename: Lakshmanaswamy
authors.initials: L
authors.lastname: Rajkumar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D031601:Azadirachta / Q000737:chemistry*; D063646:Carcinogenesis / Q000139:chemically induced / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000139:chemically induced / Q000188:drug therapy*; D008770:Methylnitrosourea; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D008770:Methylnitrosourea
keywords: Neem; angiogenesis; apoptosis; breast cancer; cell cycle