Anti-cancer activity of myricetin against human papillary thyroid cancer cells involves mitochondrial dysfunction-mediated apoptosis

Biomed Pharmacother. 2017 Jul:91:378-384. doi: 10.1016/j.biopha.2017.04.100. Epub 2017 May 2.

Abstract

Thyroid cancer is the most common endocrine malignancy and can range in severity from relatively slow-growing occult differentiated thyroid cancer to uniformly aggressive and fatal anaplastic thyroid cancer. A subset of patients with papillary thyroid cancer present with aggressive disease that is refractory to conventional treatment. Myricetin is a flavonol compound found in a variety of berries as well as walnuts and herbs. Previous studies have demonstrated that myricetin exhibits anti-cancer activity against several tumor types. However, an anti-cancer effect of myricetin against human papillary thyroid cancer (HPTC) cells has not been established. The present investigation was undertaken to gain insights into the molecular mechanism of the anti-cancer activity of myricetin against HPTC cells. We examined the cytotoxicity, DNA damaging, and cell cycle arresting activities of myricetin using SNU-790 HPTC cells. We found that myricetin exhibited cytotoxicity and induced DNA condensation in SNU-790 HPTC cells in a dose-dependent manner. Moreover, myricetin up-regulated the activation of caspase cascades and the Bax:Bcl-2 expression ratio. In addition, myricetin induced the release of apoptosis-inducing factor (AIF) and altered the mitochondrial membrane potential. Our results suggest that myricetin induces the death of SNU-790 HPTC cells and thus may prove useful in the development of therapeutic agents for human thyroid cancers.

Keywords: Apoptosis; Caspase activation; Human papillary thyroid cancer; Myricetin.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Apoptosis Inducing Factor / metabolism
  • Carcinoma, Papillary / drug therapy*
  • Carcinoma, Papillary / pathology*
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Flavonoids / chemistry
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use*
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / pathology*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • Apoptosis Inducing Factor
  • Flavonoids
  • bcl-2-Associated X Protein
  • myricetin
  • Caspases