title: Kahweol induces apoptosis by suppressing BTF3 expression through the ERK signaling pathway in non-small cell lung cancer cells.
abstract: Kahweol, a diterpene molecule, has antiproliferative effects on several types of human cancer cells, but whether it has apoptotic effect in non-small cell lung cancer (NSCLC) is not known. To explore this possibility, we incubated cells from two NSCLC cell lines, NCI-H358 and NCI‑H1299, with different concentrations of kahweol and used the MTS assay, DAPI staining, propidium iodide staining, Annexin V staining, immunocytochemical test, and western blot analysis to characterize this molecule and the signaling pathway underlying its effects. The kahweol-treated cells showed significantly decreased cell viability, increased nuclear condensation, and an increased number of Annexin V-positive NSCLC cells. Suppression of basic transcription factor 3 (BTF3) was followed by apoptosis induced by kahweol via the ERK-mediated signaling pathway in a dose- and time-dependent manner. In addition, kahweol modulated the protein expression of BTF3 genes involved in cell-cycle regulation and apoptosis-related proteins, resulting in apoptotic cell death. Our results collectively indicated that kahweol inhibited the proliferation of NSCLC cells through ERK-mediated signaling pathways and the downregulation of BTF3.
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, BK21 Plus, Chonbuk National University, Jeonju, Jeolla 561‑756, Republic of Korea.
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jeon
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, BK21 Plus, Chonbuk National University, Jeonju, Jeolla 561‑756, Republic of Korea.
authors.forename: Woong
authors.initials: W
authors.lastname: Bang
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, BK21 Plus, Chonbuk National University, Jeonju, Jeolla 561‑756, Republic of Korea.
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, BK21 Plus, Chonbuk National University, Jeonju, Jeolla 561‑756, Republic of Korea.
authors.forename: Ra Ham
authors.initials: RH
authors.lastname: Lee
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon, Republic of Korea.
authors.forename: Seok-Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Konyang University, Seo, Daejeon, Republic of Korea.
authors.forename: Minseok S
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongsang 790‑834, Republic of Korea.
authors.forename: Seon-Min
authors.initials: SM
authors.lastname: Park
authors.affiliation: Pohang Center for Evaluation of Biomaterials, Pohang, Gyeongsang 790‑834, Republic of Korea.
authors.forename: Jae-Cheon
authors.initials: JC
authors.lastname: Shin
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon, Gyeonggi, Republic of Korea.
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Chung
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon, Gyeonggi, Republic of Korea.
authors.forename: Keon Bong
authors.initials: KB
authors.lastname: Oh
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and School of Dentistry, Chonbuk National University, Jeonju, Jeolla, Republic of Korea.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Seo
authors.affiliation: Department of Applied Bioscience, CHA University, Seongnam, Gyeonggi 463-836, Republic of Korea.
authors.forename: Sungho
authors.initials: S
authors.lastname: Ko
authors.affiliation: Department of Pharmacy, College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Mokpo, Jeolla 534-729, Republic of Korea.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, BK21 Plus, Chonbuk National University, Jeonju, Jeolla 561‑756, Republic of Korea.
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Chae
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D018890:Chemoprevention; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009687:Nuclear Proteins / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D004224:Diterpenes; D009687:Nuclear Proteins; D014157:Transcription Factors; C063552:transcription factor BTF3; C053401:kahweol; D048049:Extracellular Signal-Regulated MAP Kinases