title: Tectorigenin ablates the inflammation-induced epithelial-mesenchymal transition in a co-culture model of human lung carcinoma.
abstract: OBJECTIVE
  Tumors not only manage to escape from the host immune system, but they effectively contrive to benefit from infiltrating immune cells by modifying their functions so as to create a pro-inflammatory microenvironment favorable for tumor progression and metastasis. In this study we investigated if tectorigenin could suppress lung cancer-induced pro-inflammatory response generated from monocytes.
  
  
  METHODS
  A549:THP1 co-culture model was set-up favoring release of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α). Effect of tectorigenin on A549 imparted invasive phenotype of A549:THP-1 co-culture was monitored by cytokine release from monocytes, and metastasis/epithelial-mesenchymal transitiom (EMT) in A549 cells.
  
  
  RESULTS
  In a contact A549:THP1 co-culture model, THP-1 cells were activated by A549 cells favoring secretion of pro-inflammatory cytokines, TNF-α and IL-6. However, priming of A549 cells with tectorigenin for 24h repressed A549 cell-induced secretion of TNF-α and IL-6 by THP-1 cells. Tectorigenin induced change in functional phenotype of A549 cells rendered THP-1 cells non-responsive for the secretion of IL-6 and TNF-α in a contact co-culture setup. Additionally, conditioned media from this non-responsive A549:THP-1 co-culture suppressed metastatic potential of A549 cells as confirmed by the wound healing and transwell migration assays. These finding were further corroborated by decrease in expression of Snail with a concomitant increase in E-cadherin, the two signature markers of EMT.
  
  
  CONCLUSIONS
  These results clearly demonstrate the therapeutic potential of tectorigenin to prevent lung cancer elicited inflammatory and pro-metastatic response in monocytes and warrants further investigations to elucidate its mechanism of action.
authors.affiliation: Department of Biotechnology, University of Kashmir, Srinagar, J and K, India.
authors.forename: Asif
authors.initials: A
authors.lastname: Amin
authors.affiliation: Department of Biotechnology, University of Kashmir, Srinagar, J and K, India.
authors.forename: Taseem A
authors.initials: TA
authors.lastname: Mokhdomi
authors.affiliation: Department of Biotechnology, University of Kashmir, Srinagar, J and K, India.
authors.forename: Shoiab
authors.initials: S
authors.lastname: Bukhari
authors.affiliation: Department of Biotechnology, University of Kashmir, Srinagar, J and K, India.
authors.forename: Sajad H
authors.initials: SH
authors.lastname: Wani
authors.affiliation: Department of Biotechnology, University of Kashmir, Srinagar, J and K, India.
authors.forename: Asrar H
authors.initials: AH
authors.lastname: Wafai
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, J and K, India.
authors.forename: Ghulam Nabi
authors.initials: GN
authors.lastname: Lone
authors.affiliation: Hybridoma Lab, National Institute of Immunology, New Delhi, India.
authors.forename: Ayub
authors.initials: A
authors.lastname: Qadri
authors.affiliation: Department of Biotechnology, University of Kashmir, Srinagar, J and K, India. Electronic address: raies@kashmiruniversity.ac.in.
authors.forename: Raies A
authors.initials: RA
authors.lastname: Qadri
mesh_terms: D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D015850:Interleukin-6 / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology* / Q000517:prevention & control; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D015820:Cadherins; D016207:Cytokines; D015850:Interleukin-6; D007529:Isoflavones; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C120039:tectorigenin
keywords: Co-culture model; E-cadherin; Snail; Tectorigenin