Chang Seung-Hee, Lee Ah Young, Yu Kyeong-Nam, Park Jongsun, Kim Kwang Pyo, Cho Myung-Haing
Chemotherapy. 2016;61(6):304-12. doi: 10.1159/000445044. Epub 2016 Apr 22.
Mitochondria have emerged as a major target for anticancer therapy because of their critical role in cancer cell survival. Our preliminary works have suggested that dihydroergotamine tartrate (DHE), an antimigraine agent, may have effects on mitochondria.
We examined the effect of DHE on the survival of several lung cancer cells and confirmed that DHE suppressed diverse lung cancer cell growth effectively. To confirm whether such effects of DHE would be associated with mitochondria, A549 cells were employed for the evaluation of several important parameters, such as membrane potential, reactive oxygen species (ROS) generation, apoptosis, ATP production and autophagy.
DHE decreased membrane permeability, increased ROS generation as well as apoptosis, and disturbed ATP production. Eventually, mitophagy was activated for damaged mitochondria.
Taken together, our findings demonstrate that DHE induces lung cancer cell death by the induction of apoptosis and mitophagy, thus suggesting that DHE can be developed as an anti-lung cancer therapeutic agent.
线粒体因其在癌细胞存活中的关键作用，已成为抗癌治疗的主要靶点。我们的前期研究表明，抗偏头痛药物酒石酸二氢麦角胺（DHE）可能对线粒体有影响。
我们检测了DHE对几种肺癌细胞存活的影响，并证实DHE能有效抑制多种肺癌细胞的生长。为了确定DHE的这些作用是否与线粒体有关，我们使用A549细胞评估了几个重要参数，如膜电位、活性氧（ROS）生成、凋亡、ATP产生和自噬。
DHE降低了膜通透性，增加了ROS生成以及凋亡，并干扰了ATP产生。最终，线粒体自噬被激活以清除受损线粒体。
综上所述，我们的研究结果表明，DHE通过诱导凋亡和线粒体自噬诱导肺癌细胞死亡，因此提示DHE可被开发为一种抗肺癌治疗药物。
