title: So-Cheong-Ryong-Tang induces apoptosis through activation of the intrinsic and extrinsic apoptosis pathways, and inhibition of the PI3K/Akt signaling pathway in non-small-cell lung cancer A549 cells.
abstract: BACKGROUND
  So-Cheong-Ryong-Tang (SCRT), a traditional Korean medicine containing eight species of medicinal plant, has been used to treat patients with bronchial asthma and allergic rhinitis for hundreds of years; however, its anti-cancer potential is poorly understood. The present study was designed to evaluate the apoptotic effect of SCRT against human non-small-cell lung cancer (NSCLC) A549 cells.
  
  
  METHODS
  The effects of SCRT on cell growth and viability were evaluated by trypan blue dye exclusion and 3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide (MTT) assays, respectively. Apoptosis was detected using 4,6-diamidino-2-phenyllindile (DAPI) staining, agarose gel electrophoresis and flow cytometry. The protein levels were determined by Western blot analysis. Caspase activity was measured using a colorimetric assay.
  
  
  RESULTS
  SCRT treatment resulted in significantly decreased A549 cell growth and viability by induction of apoptosis. SCRT induced the translocation of pro-apoptotic Bax to the mitochondria, mitochondrial membrane permeabilization, cytochrome c release from mitochondria to cytosol, and activated caspase-9 and caspase-3. SCRT also increased death receptor-associated ligands and enhanced the activation of caspase-8 and cleavage of its substrate Bid. However, the pan-caspases inhibitor significantly blocked the SCRT-induced apoptosis, suggesting that it is a caspase-dependent pathway. In addition, SCRT suppressed the phosphorylation of phosphoinositide 3-kinase (PI3K) and Akt, and treatment with a potent inhibitor of PI3K further increased the apoptotic activity of SCRT.
  
  
  CONCLUSIONS
  These findings suggest that SCRT may play its anti-cancer actions partly through a suppression of the PI3K/Akt signal pathway in A549 cells, and further in vivo studies on the potential of SCRT for prevention and therapy of NSCLCs are warranted.
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Dongeui University, 176 Eomgwangno Busanjin-gu, Busan, 614-714, Republic of Korea. parkch@deu.ac.kr.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, 52-57, Yangjeong-ro, Busanjin, Busan, 614-052, Republic of Korea. hongsh@deu.ac.kr.
authors.forename: Su Hyun
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, 102 Jejudaehak-ro, Jeju, 690-756, Republic of Korea. immunkim@cheju.ac.kr.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, 52-57, Yangjeong-ro, Busanjin, Busan, 614-052, Republic of Korea. choiyh@deu.ac.kr.|Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, 176 Eomgwangno Busanjin-gu, Busan, 614-714, Republic of Korea. choiyh@deu.ac.kr.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D008517:Phytotherapy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D045304:Cytochromes c; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053453:Caspase 9