Novel Molecular Targets of Azadirachta indica Associated with Inhibition of Tumor Growth in Prostate Cancer

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• 作者：Saswati Mahapatra (1)
  R. Jeffrey Karnes (1)
  Michael W. Holmes (2)
  Charles Y. F. Young (1)
  John C. Cheville (3)
  Manish Kohli (1)
  Eric W. Klee (4)
  Donald J. Tindall (1)
  Krishna Vanaja Donkena (1)
  
• 关键词：gene expression profiles ; neem leaf extract ; therapeutic targets and prostate cancer ; tumor models
• 刊名：The AAPS Journal
• 出版年：2011
• 出版时间：September 2011
• 年：2011
• 卷：13
• 期：3
• 页码：365-377
• 全文大小：909KB
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• 作者单位：Saswati Mahapatra (1)
  R. Jeffrey Karnes (1)
  Michael W. Holmes (2)
  Charles Y. F. Young (1)
  John C. Cheville (3)
  Manish Kohli (1)
  Eric W. Klee (4)
  Donald J. Tindall (1)
  Krishna Vanaja Donkena (1)
  
  1. Department of Urology and Biochemistry/Molecular Biology, Mayo Clinic/Foundation, Guggenheim 5-01B, 200 First Street SW, Rochester, Minnesota, 55905, USA
  2. Proteomics Research Center, Mayo Clinic, Rochester, Minnesota, USA
  3. Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA
  4. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA
  
• ISSN：1550-7416

文摘

Advanced prostate cancer has significant long-term morbidity, and there is a growing interest in alternative and complimentary forms of therapy that will improve the outcomes of patients. Azadirachta indica (common name: neem) contains multiple active compounds that have potent anti-inflammatory and anticancer properties. The present study investigates the novel targets of the anticancer activity of ethanol extract of neem leaves (EENL) in vitro and evaluates the in vivo efficacy in the prostate cancer models. Analysis of the components in the EENL by mass spectrometry suggests the presence of 2-3-dehydrosalannol, 6-desacetyl nimbinene, and nimolinone. Treatment of C4-2B and PC-3M-luc2 prostate cancer cells with EENL inhibited the cell proliferation. Genome-wide expression profiling, using oligonucleotide microarrays, revealed genes differentially expressed with EENL treatment in prostate cancer cells. Functional analysis unveiled that most of the up-regulated genes were associated with cell death, and drug metabolism, and the down-regulated genes were associated with cell cycle, DNA replication, recombination, and repair functions. Quantitative PCR confirmed significant up-regulation of 40 genes and immunoblotting revealed increase in the protein expression levels of HMOX1, AKR1C2, AKR1C3, and AKR1B10. EENL treatment inhibited the growth of C4-2B and PC-3M-luc2 prostate cancer xenografts in nude mice. The suppression of tumor growth is associated with the formation of hyalinized fibrous tumor tissue and the induction of cell death by apoptosis. These results suggest that EENL-containing natural bioactive compounds could have potent anticancer property and the regulation of multiple cellular pathways could exert pleiotrophic effects in prevention and treatment of prostate cancer.