title: Induction of apoptosis by parthenolide in human oral cancer cell lines and tumor xenografts.
abstract: OBJECTIVE
  Parthenolide (PTL), a representative sesquiterpene lactone that is responsible for medicinal properties of the feverfew, is known to modulate diverse intracellular signaling pathways, thereby exerting the tumor growth-inhibitory effects. In this study, authors attempted to examine the pro-apoptotic effects and possible biochemical mechanisms of PTL in human oral cancer cell lines and tumor xenografts.
  
  
  METHODS
  The apoptotic effects and related molecular mechanisms of PTL on oral cancer were evaluated using cell viability assay, MTS assay, DAPI staining, western blot analysis, reverse transcriptase-polymerase chain reaction, small interfering RNA transfection and nude mouse xenograft assay.
  
  
  RESULTS
  PTL treatment increased the cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP), and the nuclear fragmentation in a concentration- or time-dependent manner. PTL treatment increased Bim protein expression by enhancing the Bim mRNA expression as well as stabilizing Bim protein level. PTL treatment also induced the translocation of cytosolic Bim into the mitochondria and, more importantly, PTL-induced apoptosis was significantly attenuated, when the Bim expression was knockdown by siRNA transfection. PTL treatment also induced death receptor 5 (DR5) protein expression and this event was closely correlated with an increase in the cleavage of caspase-8 and formation of truncation of Bid (t-Bid). Finally, PTL shrunk tumor size and volume resulting from apoptotic cell death by increasing Bim and DR5 whereas there were no abnormal histopathological findings in normal organs.
  
  
  CONCLUSIONS
  This study proposes that PTL is a strong apoptotic inducer that deserves the further investigations for potential chemotherapeutic agent of human oral cancers.
authors: Department of Oral Pathology and Cancer Biology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors: Hyun-Ju
authors: HJ
authors: Yu
authors: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 314-701, Republic of Korea.
authors: Ji-Youn
authors: JY
authors: Jung
authors: Department of Dermatology and Biochemistry, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Joseph H
authors: JH
authors: Jeong
authors: Department of Oral Pathology and Cancer Biology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, Republic of Korea. Electronic address: efiwdsc@chonbuk.ac.kr.
authors: Sung-Dae
authors: SD
authors: Cho
authors: Department of Bio and Functional Food, College of Medical Science, Jeonju University, Jeonju 560-759, Republic of Korea. Electronic address: jslee11@jj.ac.kr.
authors: Jeong-Sang
authors: JS
authors: Lee
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D012717:Sesquiterpenes; C002669:parthenolide; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053181:Caspase 8
keywords: Apoptosis; Bim; Death receptor 5; Oral cancer; Parthenolide