title: Boehmenan, a lignan from the Chinese medicinal plant Clematis armandii, induces apoptosis in lung cancer cells through modulation of EGF-dependent pathways.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) is an effective molecular target for cancer treatment. Boehmenan, a lignan from the dried stems of Clematis armandii, exhibited the potent cytotoxic effects against many cancer cell lines in previous studies. However, the effects and underlying mechanism of boehmenan on non-small cell lung cancer (NSCLC) remains unclear.
  
  
  OBJECTIVE
  The present study was designed to determine the in vitro anti-cancer properties and underlying molecular mechanisms of boehmenan on A549 NSCLC cells.
  
  
  METHODS
  Cellular viability and chemoattractive properties of macrophages were investigated by using MTT and transwell migration assay, respectively. Mitochondrial membrane potential (ΔΨm), apoptotic ratio, and cell cycle were measured by flow cytometry. Protein expression was visualized by Western blot using specific antibodies.
  
  
  RESULTS
  Boehmenan concentration-dependently suppressed proliferation and induced G1 phase arrest in A549 NSCLC cells, which were accompanied by reduction of migration, colony formation and increase of apoptosis in A549 cells. In addition, boehmenan treatment markedly modulated apoptosis-related protein (p53, p21, cleaved caspase 3, and cleaved PARP) and cyclin D1 expression and induced ΔΨm collapse in a concentration dependent manner. Furthermore, boehmenan concentration-dependently inhibited EGF-induced activation of EGFR and its downstream signaling molecules, including MEK, Akt, ERK1/2, and STAT3.
  
  
  CONCLUSIONS
  Taken together, our results suggested that boehmenan-mediated anti-tumor property was mediated by modulation of mitochondria and EGFR signaling pathway in A549 NSCLC cells.
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai 201203, China ; Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Li-Long
authors.initials: LL
authors.lastname: Pan
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai 201203, China ; Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Xi-Ling
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai 201203, China ; Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Qiu-Yang
authors.initials: QY
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai 201203, China ; Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Luo
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai 201203, China ; Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai 201203, China ; Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Si-Yu
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826, Zhangheng Road, Pudong New District, Shanghai 201203, China . Electronic address: jfhu@fudan.edu.cn.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Hu
authors.affiliation: Shanghai Key Laboratory of Bioactive Small Molecules, School of Pharmacy, Fudan University, Shanghai 201203, China ; Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China . Electronic address: liuxinhua@fudan.edu.cn.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D039324:Clematis / Q000737:chemistry*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D017705:Lignans; C000611654:boehmenan; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Apoptosis; Boehmenan; Epidermal growth factor receptor; Migration; Non-small cell lung cancer cells