Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Interdisciplinary Program in Genetic Engineering, Seoul National University, Seoul, Republic of Korea.
Anticancer Res. 2020 Jan;40(1):323-333. doi: 10.21873/anticanres.13956.
BACKGROUND/AIM: Despite the Warburg effect, mitochondria play an essential role in the survival and maintenance of cancer cells. Thus, mitochondria have been considered a target for anticancer agents. Here, we identified a mitochondria-targeting anticancer agent from natural products.
Morphological and functional changes in mitochondria were determined by a fluorescence-based High Content Imaging System. Using human non-small cell lung cancer (NSCLC) cell lines (H1299, H226B, and A549), cell viability and colony formation assays, cell cycle analysis, and immunoblotting were performed to determine cytotoxic and proapoptotic effects of papuamine.
Using a natural product chemical library, we identified papuamine as an active compound to inhibit viability and ATP production of NSCLC cells. Papuamine depleted intracellular ATP by causing mitochondrial dysfunction, as indicated by the loss of the mitochondrial membrane potential and increased mitochondrial superoxide generation. Papuamine significantly inhibited viability and colony formation of NSCLC cells by inducing apoptosis.
Papuamine has a potential as a novel mitochondria-targeting anticancer agent.
背景/目的：尽管存在瓦博格效应，但线粒体在癌细胞的存活和维持中起着至关重要的作用。因此，线粒体已被视为抗癌药物的靶点。在这里，我们从天然产物中鉴定出一种靶向线粒体的抗癌剂。
通过基于荧光的高内涵成像系统来确定线粒体的形态和功能变化。使用人非小细胞肺癌（NSCLC）细胞系（H1299、H226B 和 A549），进行细胞活力和集落形成测定、细胞周期分析和免疫印迹，以确定帕普胺的细胞毒性和促凋亡作用。
使用天然产物化学文库，我们鉴定出帕普胺是一种能够抑制 NSCLC 细胞活力和 ATP 产生的活性化合物。帕普胺通过引起线粒体功能障碍来耗竭细胞内的 ATP，这表现为线粒体膜电位丧失和线粒体超氧化物生成增加。帕普胺通过诱导细胞凋亡显著抑制 NSCLC 细胞的活力和集落形成。
帕普胺具有成为新型靶向线粒体的抗癌剂的潜力。
