title: In Vitro Assessment of the Anticancer Potential of Evodiamine in Human Oral Cancer Cell Lines.
abstract: Evodiamine, a bioactive alkaloid, has been regarded as having antioxidant, antiinflammatory, and anticancer properties. In the present study, we explored the effects of evodiamine on cell growth and apoptosis in human oral cancer cell lines. Our data revealed that evodiamine significantly inhibited the proliferation of human oral cancer cells and resulted in the cleavages of PARP (poly (ADP-ribose) polymerase) and caspase-3, in addition to causing the typical characteristics of apoptosis. Evodiamine also increased Bax protein levels and caused translocation of Bax into mitochondria and Bax oligomerization. In addition, evodiamine decreased expression of myeloid cell leukemia (Mcl-1) at the transcriptional modification, and knockdown of Mcl-1 clearly resulted in an increase in expression of Bax and active Bax, resulting in induction of apoptosis. Evodiamine reduced expression of phosphorylated AKT, and LY294002 potentiated evodiamine-induced apoptosis by regulating Mcl-1 protein. Our results suggest that evodiamine induces apoptosis in human oral cancer cells through the AKT pathway. These findings provide a rationale for its clinical application in the treatment of oral cancer.
authors.affiliation: Department of Oral Pathology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeonju, 561-756, Korea.
authors.forename: Khadka
authors.initials: K
authors.lastname: Sachita
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonbuk National University, Jeonju, 561-756, Korea.
authors.forename: Yongsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Oral Pathology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeonju, 561-756, Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Yu
authors.affiliation: Department of Oral Pathology, School of Dentistry, and Institute of Oral Bioscience, Chonbuk National University, Jeonju, 561-756, Korea.
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
authors.affiliation: Food Industry Research Institute, Department of Health and Functional Food, College of Medical Science, Jeonju University, Jeonju, 560-759, Korea.
authors.forename: Jeong-Sang
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D009025:Morpholines; D009062:Mouth Neoplasms / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D002867:Chromones; C579095:MCL1 protein, human; D009025:Morpholines; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010936:Plant Extracts; D011799:Quinazolines; D051028:bcl-2-Associated X Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C049639:evodiamine; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: AKT; Bax; Mcl-1; apoptosis; evodiamine; oral cancer