title: Myricetin Induces Apoptosis of Human Anaplastic Thyroid Cancer CellsviaMitochondria Dysfunction.
abstract: Thyroid cancer is the most common endocrine malignancy, with an increasing incidence worldwide. Most thyroid cancers are well differentiated and have a favorable outcome. However, undifferentiated thyroid cancers are one of the most lethal human malignancies. Anaplastic thyroid cancer (ATC) accounts for 2% of all thyroid cancers, and its median survival rate is low. ATC is responsible for more than one-third of thyroid cancer-related deaths. Myricetin is a flavonol compound found in walnuts, herbs, and various berries and is known to induce apoptotic death of various types of cancer cells. However, an anticancer effect of myricetin against human anaplastic thyroid cancer (HATCs) cells has not been demonstrated.
  
  
  
  In the present study, the anticancer effects and mechanism of action of myricetin were examined using SNU-80 HATC cells. SNU-80 HATC cells were treated with various concentrations of myricetin and compared with untreated controls.
  
  
  
  Myricetin significantly reduced HATC cell proliferation, by approximately 70%. A substantial proportion of dead cells exhibited arrest in the sub-G1phase. Myricetin also exhibited cytotoxicity and induced DNA condensation in SNU-80 HATC cells in a dose-dependent manner. The mechanism of myricetin-induced cell death involved an increase in the activation of caspase cascades and the Bax:Bcl-2 ratio at a concentration of 100 μM. Myricetin also induced the release of apoptosis-inducing factor (AIF) from mitochondria into the cytosol and altered the mitochondrial membrane potential.
  
  
  
  Our results indicate that myricetin is a potent inducer of HATC cell death and may thus prove useful in the development of therapeutic agents for HATC.
authors.affiliation: Department of Life Sciences, BK21-plus Research Team for Bioactive Control Technology, College of Natural Sciences, Chosun University, Gwangju, Republic of Korea.
authors.forename: Sunhyo
authors.initials: S
authors.lastname: Jo
authors.affiliation: Department of Surgery, Inje University College of Medicine, Busan Paik Hospital, Busan, Republic of Korea.
authors.forename: Tae Kwun
authors.initials: TK
authors.lastname: Ha
authors.affiliation: Department of Verterinary Internal Medicine, College of Verterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Han
authors.affiliation: Department of Life Sciences, BK21-plus Research Team for Bioactive Control Technology, College of Natural Sciences, Chosun University, Gwangju, Republic of Korea.
authors.forename: Mi Eun
authors.initials: ME
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, BK21-plus Research Team for Bioactive Control Technology, College of Natural Sciences, Chosun University, Gwangju, Republic of Korea.
authors.forename: Inae
authors.initials: I
authors.lastname: Jung
authors.affiliation: Department of Verterinary Internal Medicine, College of Verterinary Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hee-Woo
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Medical Management, Kosin University, Busan, Republic of Korea.
authors.forename: Sung Kwon
authors.initials: SK
authors.lastname: Bae
authors.affiliation: Department of Life Sciences, BK21-plus Research Team for Bioactive Control Technology, College of Natural Sciences, Chosun University, Gwangju, Republic of Korea junsiklee@chosun.ac.kr.
authors.forename: Jun Sik
authors.initials: JS
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D065646:Thyroid Carcinoma, Anaplastic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D005419:Flavonoids; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C040015:myricetin; D020169:Caspases
keywords: Bax/BcL-2 ratio; Myricetin; cell cycle; human anaplastic thyroid cancer cells