甲状腺癌是最常见的内分泌恶性肿瘤之一。分化型甲状腺癌（DTC）的治疗基于甲状腺滤泡细胞对放射性碘化物（RAI）的摄取能力。DTC通常具有良好的预后。然而，在某些DTC患者中，肿瘤的去分化或某些细胞死亡机制的缺陷导致RAI抵抗。因此，仍有必要开发增强RAI敏感性的新型治疗方法。我们发现，姜黄中的活性成分姜黄素能够快速积聚于甲状腺癌细胞的粒状体中，但不影响正常上皮细胞。姜黄素处理会引发粒状体膜去极化，将粒状体包裹于溶酶体泡中，并且使粒状体的质量和蛋白质显著减少，表明姜黄素能够选择性地诱导甲状腺癌细胞进行线粒体自噬。此外，姜黄素诱导的线粒体自噬性细胞死亡及其与放射碘的协同细胞毒效应可以被自噬抑制剂3-甲基腺嘌呤（3-MA）削弱。有趣的是，姜黄素诱导线粒体自噬潜力的机制是其独特的靶向线粒体属性，它会引发僵硬肌瘤蛋白酶（SDH）活性爆发和过量的ROS产生。我们的数据表明，姜黄素能够引发线粒体功能障碍，并触发致命的线粒体自噬，进而与放射碘协同杀死甲状腺癌细胞。2023版权所有。由Elsevier Ltd.发布。

Thyroid cancer is one of the most common endocrine malignancies. Differentiated thyroid cancer (DTC) treatment is based on the ability of thyroid follicular cells to accumulate radioactive iodide (RAI). DTC generally has a good prognosis. However, tumor dedifferentiation or defect in certain cell death mechanism occurs in a subset of DTC patients, leading to RAI resistance. Therefore, developing novel therapeutic approaches that enhance RAI sensitivity are still warranted. We found that curcumin, an active ingredient in turmeric with anti-cancer properties, rapidly accumulated in the mitochondria of thyroid cancer cells but not normal epithelial cells. Curcumin treatment triggered mitochondrial membrane depolarization, engulfment of mitochondria within autophagosomes and a robust decrease in mitochondrial mass and proteins, indicating that curcumin selectively induced mitophagy in thyroid cancer cells. In addition, curcumin-induced mitophagic cell death and its synergistic cytotoxic effect with radioiodine could be attenuated by autophagy inhibitor, 3-methyladenine (3-MA). Interestingly, the mechanism of mitophagy-inducing potential of curcumin was its unique mitochondria-targeting property, which induced a burst of SDH activity and excessive ROS production. Our data suggest that curcumin induces mitochondrial dysfunction and triggers lethal mitophagy, which synergizes with radioiodine to kill thyroid cancer cells.Copyright © 2023. Published by Elsevier Ltd.