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

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.