title: The pro-apoptotic role of autophagy in breast cancer.
abstract: BACKGROUND
  Autophagy is a catabolic process that has a vital role in cancer progression and treatment. Current chemotherapeutic agents, which target autophagy, result in growth inhibition in many cancer types. In this study, we examined the role of autophagy in breast cancer (BCa) patients as well as BCa cell lines.
  
  
  METHODS
  Tissue microarray was used to detect the expression of an autophagy marker, LC3B in BCa patients (normal/hyperplasia=8; grade-I=15, grade-II=84, and grade-III=27) and BCa cell lines. To modulate the activation of autophagy, we used novel herbal compound nimocinol acetate (NA) in BCa cell lines and the anticancer activity was measured by phenotypic and molecular analysis.
  
  
  RESULTS
  LC3B is highly expressed in tumours as compared with normal tissues. Activation of LC3B in NA-treated BCa (MCF-7 and MDA-MB-231) cells was evident as compared with other autophagy makers. Further, our results confirmed that NA-transcriptionally regulates LC3B (as confirmed by mRNA levels and reporter assay), which resulted in the formation of acidic autophagy vesicles and autolysosomes in BCa cells. Nimocinol acetate inhibited mTOR-mediated pro-survival signalling that resulted in inhibition of growth in BCa cells without affecting normal breast epithelial cells. Downregulation of LC3B expression by siRNA significantly inhibited the anticancer effects of NA in BCa cells.
  
  
  CONCLUSIONS
  Together, our results suggest that LC3B is highly expressed in BCa tissues and increasing the threshold of LC3B activation dictates the pro-apoptotic function, which in turn, suppresses the growth of BCa cells. Nimocinol acetate could be a potential agent for treatment of BCa.
authors.affiliation: 1] Department of Biomedical Sciences, Paul L Foster school of Medicine, Texas Tech University Health Sciences center, El Paso, TX, USA [2] Department of Urology, University of Louisville, KY 40202, USA.
authors.forename: S
authors.initials: S
authors.lastname: Suman
authors.affiliation: 1] Department of Biomedical Sciences, Paul L Foster school of Medicine, Texas Tech University Health Sciences center, El Paso, TX, USA [2] Department of Urology, University of Louisville, KY 40202, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Das
authors.affiliation: Department of Biomedical Sciences, Paul L Foster school of Medicine, Texas Tech University Health Sciences center, El Paso, TX, USA.
authors.forename: R
authors.initials: R
authors.lastname: Reddy
authors.affiliation: Department of Biomedical Sciences, Paul L Foster school of Medicine, Texas Tech University Health Sciences center, El Paso, TX, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Nyakeriga
authors.affiliation: Department of Biomedical Sciences, Paul L Foster school of Medicine, Texas Tech University Health Sciences center, El Paso, TX, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Luevano
authors.affiliation: Division of Synthetic Organic Chemistry, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India.
authors.forename: D
authors.initials: D
authors.lastname: Konwar
authors.affiliation: Division of Synthetic Organic Chemistry, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India.
authors.forename: P
authors.initials: P
authors.lastname: Pahari
authors.affiliation: 1] Department of Biomedical Sciences, Paul L Foster school of Medicine, Texas Tech University Health Sciences center, El Paso, TX, USA [2] Department of Urology, University of Louisville, KY 40202, USA.
authors.forename: C
authors.initials: C
authors.lastname: Damodaran
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D046888:Tissue Array Analysis; D014162:Transfection; D014315:Triterpenes / Q000494:pharmacology
chemical_list: C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; D014315:Triterpenes; C000592931:nimocinol acetate